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Vol. 10, Issue 3, 277-292, March 2000
REVIEW
A Phenotype Map of the Mouse X Chromosome: Models for Human X-linked Disease
Yvonne
Boyd,1,4
Helen J.
Blair,2
Pamela
Cunliffe,3
Walter K.
Masson,1 and
Vivienne
Reed
Medical Research Council (MRC) Mammalian Genetics Unit,
Harwell, Oxon OX11 0RD UK
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ABSTRACT |
The identification of many of the transcribed genes in man and mouse
is being achieved by large scale sequencing of expressed sequence tags
(ESTs). Attention is now being turned to elucidating gene function and
many laboratories are looking to the mouse as a model system for this
phase of the genome project. Mouse mutants have long been used as a
means of investigating gene function and disease pathogenesis, and
recently, several large mutagenesis programs have been initiated to
fulfill the burgeoning demand of functional genomics research.
Nevertheless, there is a substantial existing mouse mutant resource
that can be used immediately. This review summarizes the available
information about the loci encoding X-linked phenotypic mutants and
variants, including 40 classical mutants and 40 that have arisen from
gene targeting.
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INTRODUCTION |
Mammalian X-linked traits are easily recognized by their inheritance
patterns and their mode of expression. Whereas hemizygous males carry one copy of X-linked loci and suffer from the full effect
of any mutation, heterozygous females carry two copies and have a
phenotype that reflects the relative expression, as determined by
X-inactivation status, of the mutated and normal copies of the gene
(Lyon 1999 ). The X chromosome is also unusual in that X linkage of
genes is almost totally conserved in eutherian mammals (Ohno 1973).
Therefore, disorders that are X linked in man are also X linked in the
mouse, which leads to the ready identification of mouse models of human
X-linked disease. The existing mouse mutant resource, which comprises
well over 1000 different stocks and strains, has been exploited to
investigate gene function and disease pathogenesis associated with
X-linked and autosomal loci (Paigen 1995; Bedell et al.
1997)5. The past decade has seen a revolution in the ability
to deliberately introduce mutations into mouse genes by homologous
recombination (Fisher 1997; Müller 1999; Roths et al. 1999) and,
as a result, the number of mouse X-linked traits has doubled. Although
there are earlier reviews (Davisson 1987; Miller 1990), no
comprehensive summary of existing mouse X-linked phenotypes has been
published recently. The primary aim of this review is to describe the
current status of the phenotype map of the mouse X chromosome for those working in the field of genome research with an interest in X-linked disease.
Analyzing mouse mutants at the molecular and phenotypic level is one of
the most powerful ways of understanding gene function in mammals. Apart
from a few notable exceptions, in which mutations exist in mouse genes
whose homologs are known to be responsible for human disease, there are
considerable phenotypic similarities between the mouse and human
disorders, and the mutant mouse provides an animal model for
understanding disease pathogenesis and for assessing therapeutic
regimes. Therefore, it is likely that most of the remaining mouse
phenotypes will provide a valuable resource for identifying the
molecular basis of a homologous human disease.
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Comparative Map of the Human and Mouse X Chromosomes |
The initial stage of assessing and identifying mouse models for
human disease from the existing mouse mutant resources involves careful
characterization of the phenotype associated with the mutant locus and
predicting the position of its human homolog on the man-mouse
comparative map.
The mapping of >130 conserved loci on the X chromosomes of both
mouse and man (Boyd et al. 1998, 1999) has confirmed the prediction that X linkage of genes is preserved in mammals (Ohno 1973). However, when the relative positions of loci on the human and mouse X
chromosomes are compared, it can be seen that subchromosomal blocks of
homologous loci have been rearranged with respect to each other during
the 80 million years of evolutionary time that separate the two
species. It is important to understand these rearrangements fully,
because an identical comparative map position is an important criterion for identifying and confirming mouse models for human genetic disease.
More than a decade ago, five distinct homologous blocks of loci or
conserved segments were acknowledged as sharing homology on both the
human and mouse X chromosomes (Searle et al. 1987, 1989; Amar et al.
1988; see Fig.1 and Table 1 for the current status of
the comparative map). The human X
chromosome long arm (Xq) was recognized as being split into two major
blocks on the mouse X chromosome. There are only two minor
modifications to this Xq comparative map, the identification of a
600-kb inversion around Xist (Rougelle and Avner 1996) and the
mapping of the synaptobrevin like locus (Sybl1) to the
proximal region of the mouse X chromosome (D'Esposito et al. 1997). In
contrast, it soon became apparent that the three conserved segments
thought to comprise the human X chromosome short arm (Xp) could be
apportioned into five major and four minor conserved segments on the
mouse X chromosome (Laval and Boyd 1993; Blair et al. 1994, 1995,
1998b; Blaschke and Rappold 1997). Twelve conserved segments have now
been identified on the man-mouse X chromosome comparative map (Fig.1),
and additional regions of homology may be defined as conserved genes
are mapped to a higher resolution (Ehrmann et al. 1998). Nevertheless,
for most of the X chromosome, once the position of a locus is known on
the human X chromosome, its position on the mouse X chromosome can be
predicted with reasonable accuracy and vice versa. The evolutionary
breakpoint regions remain the only areas of uncertainty and these,
because they have been subjected to multiple rearrangements during
evolution, can be expected to have a complex structure and this has
been borne out by recent mapping data (Dinulos et al. 1996; Blair et
al. 1998b; Disteche et al. 1998). Over 130 genes and conserved loci
have been regionally mapped on both the human and mouse X chromosomes
and form the framework for constructing the comparative map (Table 1).
This map has been invaluable in identifying human diseases and
candidate gene loci for many of the classical mutants that have been
recovered from mouse colonies over the years.
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Figure 1
The comparative phenotype map of the human and mouse X chromosomes.
Each conserved segment, in which the order of loci is the same in mouse
and man, is indicated by a colored rectangle. The loci that define each
segment are given in Table 1; note that the order of segments
1, 2, and 3 has not been established and is
arbitrary. The segments are numbered from 1-12 from the
centromere to the telomere on the mouse X chromosome and the order of
loci indicated by an arrow alongside each block. The hatched region
within segment 9 represents the 600-kb region that is inverted
around the Xist locus (see text). The centromeric regions are
indicated by black and white hatched rectangles; there is, as yet, no
known evidence for evolutionary conservation of centromeric sequences
between mouse and man. The Xp pseudoautosomal region, which has a
complex evolutionary history (Blaschke and Rappold 1997), is not
included because it is outside the scope of this review, as loci in
this region do not exhibit X-linked inheritance. Classical mutants
carrrying spontaneous and induced mutations and variants (Table 2) are
indicated on the mouse X chromosome, and targeted mutations (Table 3)
are positioned on the human X chromosome for clarity. Names in black
text are (1) known to have an X-linked inheritance pattern but have not
been positioned on the X (e.g., Ie, It), or (2) have
not been subjected to high-resolution mapping (e.g., Bw1, the
black line indicates the probable region in which the locus lies), or
(3) have been mapped to evolutionary breakpoint positions and therefore
the position of the human homolog cannot be defined (e.g.,
exma, Bhd, wf). For those traits marked with
an asterisk (*), the gene responsible is not known; for all other
traits the underlying lesion has been defined.
a(Ir) Immune response genes that are X linked (see
Table 2 footnote).
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Spontaneous and Induced X-Linked Mouse Mutants and Variant Traits |
Thirty-eight X-linked mouse-independent visible phenotypes covering
a wide range of traits are reported in the literature (Table 2; Fig.
2).
Most of these phenotypes have arisen spontaneously in mouse colonies or
among the large numbers of mice used in mutagenesis experiments (George
et al. 1994). The paucity of induced X-linked mutations is probably due
to that fact that most novel mutations have been sought in the
F1 progeny of mutagenized males and as a result, only those
X-linked mutations that have a phenotypic effect in heterozygous
females are identified. Some attempts were made to obtain sex-linked
recessive lethals by identifying abnormal sex ratios in the offspring
of F1 females produced in classical mutagenesis experiments
(Searle et al. 1964). Recessive mutations, such as sex-linked fidget,
arose in experiments like these (Lyon et al. 1981b; Phippard et al. 2000).
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Figure 2
Examples of spontaneous and induced X-linked traits in the mouse.
(A,B) Males carrying the greasy (Gs)
(A) and harlequin (Hq) (B) mutations;
neither of the genes responsible has been cloned. (C) A
heterozygous female carrying the broad-headed (Bhd) mutation,
which is associated with a craniofacial anomaly, note the unusually
short and broad snout. Comparative mapping has shown that Bhd
cannot be a model for FGD1 or ATRX, but it remains an interesting
skeletal mutant in which males have multiple ossification anomalies and
die shortly after birth (V. Reed and Y. Boyd, in prep.). (D) A
heterozygous female carrying a mutation at one of the mottled
(Mo) alleles associated with death between birth and weaning
of affected males (Atp7aMo-10H). The mosaic coat can
be clearly seen, in which hypopigmented areas represent populations of
cells carrying the mutant allele and the normally pigmented (brown)
areas represent areas of cells carrying the wild-type allele. Details
of the phenotypes and references describing each of these mutants are
given in Table 2.
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For most of the recovered mutations, only a single mutant allele is
available for analysis, limiting the value of the mouse as a model for
X-linked human disease, which is often associated with a high number of
different new mutations (Rossiter and Caskey 1991). However, where
several alleles exist, the mouse provides an ideal tool for studying
the phenotypic effects of different mutations in the same gene on an
identical genetic background. Over 20 alleles, associated with
differing phenotypes have been recovered at the mouse mottled locus and
these provide a useful paradigm for using the mouse to study human
disease (Cunliffe 1999).
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Mottled: A Paradigm for Mouse Models for Human X-Linked Disease |
For many years, the mottled mouse has been recognized as a model for
Menkes disease (MD), and in both species, a range of mutations has been
found in the gene encoding the copper transporter ATP7A
(Cecchi et al. 1997; Reed and Boyd 1997; Tümer et al. 1997). Affected mice and human patients show a similar and variable course of
disease with the main features being growth retardation, neurological and connective tissue abnormalities, peculiar hair and hypopigmentation (Danks 1986; Tümer and Horn 1997; Fig. 2D). Mutations that have a
mild phenotypic effect in the mouse, such as the splice-site lesion
leading to the production of both normal and aberrant transcripts in
mottled blotchy, seem to be of a similar type to those associated with
occipital horn syndrome (OHS, a mild allele of MD). In both man and
mouse, this type of mutation is associated mainly with connective
tissue problems (Das et al. 1995). However, there are significant
differences between man and mice in the type of molecular lesions
associated with the more severe phenotypes. The classical MD phenotype
is mainly associated with nonsense or frameshift mutations and there is
also a substantial proportion (~20%) of patients with gross
deletions covering varying proportions of the ATP7A-coding region. In
the mouse, the largest known deletion, which covers exons 11-14
(Cunliffe 1999), is in frame, and no nonsense or frameshift mutations
have been reported to date. This fact demonstrates that caution must be
taken when assessing potential therapies with mottled mice as animal
models. The most striking phenotypic difference is that MD patients,
with what might be expected to be null mutations at ATP7A, survive
until birth, whereas over half of the mottled alleles are associated
with prenatal lethality of males sometime after mid gestation. It has
long been thought that the mottled mutations causing early postnatal
death are the most appropriate model for classical MD in which affected boys die in the first few years of life. However, recent evidence has
shown that in the mouse, Atp7a mutations most similar to those seen in
classical MD cause prenatal death (Cunliffe 1999; P. Cunliffe, V. Reed,
and Y. Boyd, in prep.). Therefore, at the level of cellular copper
processing, mottled alleles associated with prenatal lethality may
provide a better model. This is particularly important in light of the
varied response of MD patients to copper histidine treatment
(Tümer and Horn 1997).
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Using the Mouse to Identify the Genes Responsible in X-Linked
Dominants Associated with Intrauterine Male Lethality |
A further interesting picture has emerged from studies on mouse
mutants as possible models for X-linked dominant disease, which,
because they are associated with prenatal lethality of males, are
difficult to position accurately on the human X chromosome. Disorders
associated with the lethality of males in utero are probably caused by
lesions in genes that have important developmental roles and that may
be conserved in man and mouse. In the mouse, the relative ease of
high-resolution mapping renders the genes responsible amenable to
positional cloning. Recently, an interesting association between sterol
biosynthesis and skeletal defects has been revealed by the
identification of the underlying molecular lesions in the Bpa,
Str, and Td mutants, which are all associated with
skeletal and skin anomalies in heterozygous females (Table 2).
Mutations in the 3 -hydroxysteroid dehydrogenase Nsdhl
were first found in several independently derived Bpa and
Str mutants, which were shown to be allelic, although there
are differences in the severity of the phenotype (Liu et al. 1999). The
Bpa mouse was suggested originally as a mouse homolog of CPDX2
as both display-striated hyperkeratosis and skeletal abnormalities
including short stature, rhizomelic shortening of the limbs, epipyhseal
stippling, and craniofacial anomalies (Happle 1983). However, a more
detailed phenotypic analysis of Td has revealed that it also
has many of these features and Td was discovered to be a model
for CPDX2 when mutations in the sterol isomerase Ebp were discovered in
Td and CPDX2 patients (Braverman et al. 1999; Derry et al.
1999). Thus, the Bpa/Str alleles and Td mice provide
tools to investigate the relationship between sterol biosynthesis,
intrauterine death of males, and the skin and skeletal defects seen in
heterozygous females.
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X-Linked Phenotypes Associated with Mutations Introduced by
Gene Targeting |
There are now as many mouse X-linked phenotypes introduced
deliberately by gene targeting than have been recovered over the years
in mouse colonies. Approximately one-half of the targeted genes are
implicated in overt human disease and have been ablated to create
models for understanding gene function and disease pathogenesis (Table
3). Some of these genes have shown
comparable phenotypes in the mouse, such as the targeted disruption of
genes encoding factor VIII and IX, which have provided excellent mouse
models for studies on haemophilia A and B (Bi et al. 1995; Wang et al. 1997). Others exhibit some, but not all, aspects of the corresponding human disease; for example, there is an impaired humoral immune response in CD40 ligand-deficient mice, but they do not develop full-blown hyperIgM syndrome (Renshaw et al. 1994). In the future, mouse models carrying defined molecular lesions identical to those found in human disease can be provided by gene-targeting technology. In
conjunction with the production of a series of different mutations in
the same target gene, as has been done at the autosomal Fgf8 locus by Meyers et al. (1998), the availability of engineered mouse
models relevant to human disease can only increase.
Other mutants have been created to investigate the potential functions
and the phenotypic consequence of a deficiency in the targeted gene.
Some of these studies have revealed interesting clinical effects in
mice with potential applications for studying complex human disorders,
for example the demonstration that a lack of biglycan leads to
osteoporosis (Xu et al. 1998). Other gene disruptions have also proven
to be highly informative in understanding gene function, for example,
the targeting of the Xist locus demonstrated its vital role in
the X-inactivation process (Penny et al. 1996; Marahens et al. 1997).
Until stable female embryonic stem cell lines are widely available and
can be transmitted to the germ line with a high frequency, one problem
that remains with the targeted disruption of X-linked genes is the
study of those genes that are potentially lethal in males. Genes may be
dispensable in stem cells but essential for embryonic development, as
is the case with the methyl-CpG-binding protein Mecp2 (Tate et al.
1996). The Mecp2 knockout mice are particularly interesting in light of
the recent revelation that the X-linked dominant neurological disorder
Rett syndrome is associated with MECP2 mutations (Amir et al.
1999). The problem of early lethality preventing the recovery of mice
carrying targeted mutations of X-linked genes can be partially
circumvented by the production of conditional knockouts, in which
ablation or modification of the gene of interest is engineered on a
temporal or tissue-specific basis (for review, see Müller 1999;
Roths et al. 1999). Tarutani et al. (1997) used this approach to
demonstrate that the X-linked Piga gene plays an important
role in skin development.
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X Inactivation and Analysis of the Phenotypic Variation Associated
with Heterozygous Females |
Mice carrying X-linked mutations can also be used as tools to
investigate the influence of cellular mosaicism associated with X-inactivation patterns in different tissues on the phenotype. X
inactivation occurs early in mammalian female development and results
in the transcriptional silencing of one of the two X chromosomes, at
random, in every somatic cell (Lyon 1999). As a consequence, females
heterozygous for X-linked coat mutations such as mottled have a
variegated coat pattern resulting from the two cell populations, one
expressing the mutant allele and the other expressing the wild-type
allele (Fig. 2D). Because the number of cells at the time of X
inactivation is small, and the choice of which X chromosome is
inactivated is usually random, considerable differences are seen
between females in the relative sizes of the two cell populations; this
manifests as a variation in the severity of the phenotype between
female mice carrying the same mutation. For some X-linked mutations,
cellular mosaicism is a benefit with the population of cells expressing
the normal allele, providing enough of the normal gene product to
permit a normal phenotype to develop, for example, in the sf
or spf mutations (DeMars et al. 1976; Lyon et al. 1990).
Another possibility is that growth competition between the two cell
populations may result in the virtual elimination of the cells
expressing the mutant allele (Ogura et al. 1998). In this situation,
the resultant skewed X-inactivation pattern provides heterozygous
females with a normal, or mild, phenotype.
Traditionally, X-inactivation patterns in mice have been investigated
in the coat by the observation of doubly heterozygous female mice
produced when the mutation is bred to well-characterized coat mutants,
such as the mottled blotchy or tabby mutants. In humans, approaches
that exploit the differences in DNA methylation between the inactive
and active X chromosomes are most widely used to study X-inactivation
patterns in heterozygous females (Belmont 1996). In the mouse,
extensive studies of the X-inactivation patterns can be achieved
because of the availability of tissues from several replica
heterozygotes at a range of times in development on a constant genetic
background. Techniques such as the single nucleotide primer extension
(SNuPE) assay have been used to quantitatively measure the relative
expression from the two X chromosomes in females heterozygous for
X-linked mutations (Greenwood et al. 1997; Ogura et al. 1998). Further,
the X-linked LacZ transgenic mice created by Tam and Tan
(1992) have great potential for the study of X-inactivation patterns in
heterozygous females as the transgene is subject to the inactivation
process. When the lacZ reporter is present on only one of the
X chromosomes of a female heterozygous for an X-linked mutation, the
-galactosidase activity is limited to cells with only that X
chromosome active. Therefore, the distribution of cells expressing the
mutant allele in a heterozygous female can be studied and insights into
the mode of action of the normal X-linked gene product can be provided
by the analysis of the phenotype and the X-inactivation pattern of
heterozygous females. In our laboratory, such studies are under way on
the Li, Stpy, and Td mutants.
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Future Progress |
The 80 X-linked phenotypes that have been reported in the laboratory
mouse correspond to mutations in approximately half of the cloned X
chromosomal genes. Most of these traits are associated with mutations
in known genes and are of immediate value as animal models for human
X-linked diseases. However, they represent <5% of the probable
number of X-linked genes and the phenotype map of the mouse X
chromosome is still sparse. Alternative methods will be needed to
provide the detailed phenotype maps worthy of complementing the
encyclopedias of mouse genes that are being developed (Marra et al.
1999). Although several laboratories are attempting to increase the
size of the mouse mutant resource (Justice et al. 1997; You et al.
1997; deAngelis and Balling 1998; Schimenti and Bucan 1998; Zheng et
al. 1999), no plans appear to have been made to screen systematically
the progeny of F1 females carrying mutagenized X chromosomes
for X-linked traits. Without such a specific effort, it will be
interesting to see whether the number of X-linked mutant stocks will
increase to meet the needs and interests of groups trying to understand
the roles of X-linked genes in health and disease.
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ACKNOWLEDGMENTS |
We thank Kevin Glover for help in producing Figure 2. This work was
supported by the MRC of Great Britain.
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FOOTNOTES |
Present addresses:
1Institute for Animal Health,
Compton, Newbury RG20 7NN, UK;
2Department of Physiological
Sciences, Medical School, Framlington Place, University of Newcastle,
Newcastle Upon Tyne NE2 4HH, UK;
3Department of Medicine,
Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
4
Corresponding author.
E-MAIL yvonne.boyd{at}bbsrc.ac.uk; FAX 00 44 1635 577237.
5
A comprehensive list of international mouse strain
resources, developed jointly by the UK MRC laboratory at Harwell and
the USA Jackson Laboratory (Eppig and Strivens 1999), and a list of strains available at the newly established European Mouse Mutant Archive (EMMA) in Italy, can be accessed via the World Wide Web at
http://ismr.har.mrc.ac.uk; http://www.emma.cnr.it.
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REFERENCES |
-
Alexander, C.M. and
Z. Werb.
1992.
Targeted disruption of the tissue inhibitor of metalloproteinases gene increases invasive behaviour of primitive mesenchymal cells derived from embryonic cells in vitro.
J. Cell Biol.
118:
727-739[Abstract/Free Full Text].
-
Amar, L.C.,
L. Dandalo,
A. Hanauer,
A. Ryder-Cook,
D. Arnaud,
J-L. Mandel, and
P. Avner.
1988.
Conservation and re-organisation of loci on the mammalian X chromosome; a molecular framework for the identification of homologous regions in man and mouse.
Genomics
22:
220-230[CrossRef].
-
Amir, R.E.,
I.B. Van den Veyver,
M. Wanm,
C.Q. Tran,
U. Francke, and
H.Y. Zhogbi.
1999.
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
Nat. Genet.
23:
185-188[CrossRef][Medline].
-
Araki, E.,
K. Nakamura,
K. Nakao,
S. Kameya,
O. Kobayashi,
I. Nonaka,
T. Kobayashi, and
M. Katsuki.
1997.
Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy.
Biochem. Biophys. Res. Comm.
238:
492-497[CrossRef][Medline].
-
Arrandale, J.M.,
A. Gore-Willse,
S. Rocks,
J.M. Ren,
J. Zhu,
A. Davis,
J.N. Livingston, and
D.U. Rabin.
1996.
Insulin signaling in mice expressing reduced levels of Syp.
J. Biol. Chem.
271:
21353-21358[Abstract/Free Full Text].
-
Bakker, C.E.,
C. Verheij,
R. Willemsen,
R. van der Helm,
F. Oerlemans,
M. Vermey,
A. Bygrave,
A.T. Hoogeveen,
B.A. Oostra,
E. Reyniers
1994.
FMR1 knockout mice
 A model to study fragile-X mental retardation.
Cell
78:
23-33[CrossRef][Medline]. -
Barber, B.R.
1971.
Research News.
Mouse NewsLett.
45:
34-35.
-
Barra, J.
1990.
An X-linked recessive mutation producing cleft palate, crooked tail, and polydactyly in mice.
J. Hered.
81:
388-392[Abstract/Free Full Text].
-
Bedell, M.A.,
N.A. Jenkins, and
N.G. Copeland.
1997.
Mouse models of human disease.
Genes & Dev.
11:
1-43[Free Full Text].
-
Belmont, J.W.
1996.
Genetic control of X inactivation and processes leading to X-inactivation skewing.
Am. J. Hum. Genet.
58:
1101-1108[Medline].
-
Berger, W.,
D. van de Pol,
D. Bachner,
F. Oerlemans,
H. Winkens,
H. Hameister,
B. Wieringa,
W. Hendriks, and
H.-H. Ropers.
1996.
An animal model for Norrie disease (ND); gene targeting of the mouse ND gene.
Hum. Mol. Genet.
5:
51-59[Abstract/Free Full Text].
-
Bi, L.,
A.M. Lawler,
S.E. Antonarakis,
K.A. High,
J.D. Gearhart, and
H.H. Kazazian.
1995.
Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A.
Nat. Genet.
10:
119-121[CrossRef][Medline].
-
Blair, H.J.,
V. Reed,
S.H. Laval, and
Y. Boyd.
1994.
New insights into the man-mouse comparative map of the X chromosome.
Genomics
19:
215-220[CrossRef].
-
Blair, H.J.,
M. Ho,
A.P. Monaco,
S. Fisher,
I.W. Craig, and
Y. Boyd.
1995.
High resolution comparative mapping of the proximal region of the mouse X chromosome.
Genomics
28:
305-310[CrossRef][Medline].
-
Blair, H.J.,
E. Gormally,
I.C. Uwechue, and
Y. Boyd.
1998a.
Mouse mutants carrying deletions that encompass the genes deleted in Coffin-Lowry syndrome and lactic acidosis.
Hum. Mol. Genet.
7:
549-555[Abstract/Free Full Text].
-
Blair, H.J.,
I.C. Uwechue,
G.S. Barsh,
P.S.N. Rowe, and
Y. Boyd.
1998b.
An integrated genetic and man-mouse comparative map of the DXHXS674-Pdha1 region of the mouse X chromosome.
Genomics
48:
128-131[CrossRef][Medline].
-
Blaschke, R.J. and
G.A. Rappold.
1997.
Man to mouselessons learned from the distal end of the human X chromosome.
Genome Res.
7:
1114-1117[Free Full Text].
-
Boison, D. and
W. Stoffel.
1994.
Disruption of the compacted myelin sheath of axons of the central nervous system in proteolipid-deficient mice.
Proc. Natl. Acad. Sci.
91:
11709-11713[Abstract/Free Full Text].
-
Boyd, Y.,
H.J. Blair,
P. Cunliffe,
P. Denny,
E. Gormally, and
G.E. Herman.
1998.
Mouse Chromosome X.
Mamm. Genome
8:
S361-S377.
-
Boyd, Y.,
P. Denny,
W.K. Masson,
V. Reed, and
R. Elliott.
1999.
Mouse X chromosome.
Mamm. Genome
10:
961[CrossRef][Medline].
-
Bravermann, N.,
P. Lin,
F.F. Moebius,
C. Obie,
A. Moser,
H. Glossman,
W.R. Wilcox,
D.L. Rimoin,
M. Smith,
L. Kratz
1999.
Mutations in the gene encoding 3-hydroxysteroid-
 8,7-isomerase cause X-linked dominant Conradi-Hünerman syndrome.
Nat. Genet.
22:
291-294[CrossRef][Medline]. -
Bulfield, G.,
W.G. Siller,
P.A.L. Wight, and
K.J. Moore.
1984.
X chromosome-linked muscular dystrophy (mdx) in the mouse.
Proc. Natl. Acad. Sci.
81:
1189-1192[Abstract/Free Full Text].
-
Cases, O.,
I. Seif,
J. Grimsby,
P. Gaspar,
K. Chen,
S. Pournin,
U. Müller,
M. Auguet,
C. Babinet,
J.C. Shih
1995.
Aggressive behaviour and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA.
Science
268:
1763-1766[Abstract/Free Full Text].
-
Castigli, E.,
R. Fuleihan,
N. Ramesh,
E. Tsitsikov,
A. Tsytsykov, and
R.S. Geha.
1995.
CD40 ligand/CD40 deficiency.
Int. Arch. Allergy Immunol.
107:
37-39[Medline].
-
Cecchi, C.,
M. Biasotto,
M. Tosi, and
P. Avner.
1997.
The mottled mouse as a model for human Menkes disease: Identification of mutations in the Atp7a gene.
Hum. Mol. Genet.
6:
425-433[Abstract/Free Full Text].
-
Chapman, V.M.,
D.R. Miller,
D. Armstrong, and
C.T. Caskey.
1989.
Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice.
Proc. Natl. Acad. Sci.
86:
1292-1296[Abstract/Free Full Text].
-
Charest, N.J.,
Z. Zhou,
D.B. Lubahn,
K.E. Olsen,
E.M. Wilson, and
F.S. French.
1991.
A frameshift mutation destablizes androgen receptor RNA in the Tfm mouse.
Mol. Endocrinol.
5:
573-581[Abstract].
-
Chin, L.S.,
L. Li,
A. Ferreira,
K.S. Kosik, and
P. Greengard.
1995.
Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice.
Proc. Natl. Acad. Sci.
92:
9230-9234[Abstract/Free Full Text].
-
Cunliffe, P.
1999.
"Molecular genetic analysis of mottled mice", Ph. D. thesis. University of Oxford, Oxford, UK.
-
Dahme, M.,
U. Bartsch,
R. Martini,
B. Anliker,
M. Schachner, and
N. Mantei.
1997.
Disruption of the mouse L1 gene leads to malformations of the nervous system.
Nat. Genet.
17:
346-349[CrossRef][Medline].
-
Danks, D.M.
1986.
Of mice and men, metals and mutations.
J. Med .Genet.
23:
99-106[Abstract].
-
Das, S.,
B. Levinson,
C. Vulpe,
S. Whitney,
J. Gitschier, and
S. Packman.
1995.
Similar splicing mutations of the Menkes/mottled copper-transporting ATPase gene in occipital horn syndrome and the blotchy mouse.
Am. J. Hum. Genet.
56:
570-576[Medline].
-
Dautigny, A.,
M.-G. Mattei,
D. Morello,
P. M. Alliel,
D. Pham-Dinh,
L. Amar,
D. Arnaud,
D. Simon,
J.-F. Mattei,
J.-L. Guenet
1986.
The structural gene coding for mylein-associated proteolipid protein is mutated in jimpy mice.
Nature
321:
867-868[CrossRef][Medline].
-
Davisson, M.T.
1987.
X-linked homologies between mouse and man.
Genomics
1:
213-227[CrossRef][Medline].
-
De Angelis, M.H. and
R. Balling.
1998.
Large scale ENU screens in the mouse: Genetics meets genomics.
Mutat. Res.
400:
25-32[Medline].
-
De Mars, R.,
S.L. LeVan,
B.L. Trend, and
L.B. Russell.
1976.
Abnormal ornithine carbamoyltransferase in mice having the sparse-fur mutation.
Proc. Natl. Acad. Sci.
73:
1693-1697[Abstract/Free Full Text].
-
Derry, J.M.J.,
E. Gormally,
G.D. Means,
W. Zhao,
A. Meindl,
R.I. Kelley,
Y. Boyd, and
G.E. Herman.
1999.
Mutations in a 8-7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata.
Nat. Genet.
22:
286-290[CrossRef][Medline].
-
D'Esposito, M.,
M.R. Matarazzo,
A. Ciccodicola,
M. Strazzullo,
R. Mazzarella,
N.A. Quaderi,
H. Fujiwara,
M.S.H. Ko,
L.B. Rowe,
A. Ricco
1997.
Differential expression pattern of XqPAR-linked genes SYBL1 and IL9R correlates with the structure and evolution of the region.
Hum. Mol. Genet.
6:
1917-1923[Abstract/Free Full Text].
-
Dinulos, M.B.,
M.T. Bassi,
E.I. Rugarli,
V. Chapman,
A. Ballabio, and
C. Disteche.
1996.
A new region of conservation is defined between the human and mouse X chromosomes.
Genomics
35:
244-247[CrossRef][Medline].
-
Disteche, C.M.,
M.B. Dinulos,
M.T. Bassi,
R.W. Elliott, and
E.I. Rugarli.
1998.
Mapping of the murine Tbl1 gene reveals a new rearrangement between mouse and human X chromosomes.
Mamm. Genome
9:
1062-1064[CrossRef][Medline].
-
Dragani, T.A.,
Z.-B. Zeng,
F. Canzian,
M. Garibaldi,
M.T. Ghilarducci,
G. Manento, and
M.A. Pierotti.
1995.
Mapping of body weight loci on mouse chromosome X.
Mamm. Genome
6:
778-781[CrossRef][Medline].
-
Ehrman, I.E.,
P.S. Ellis,
S. Mazeyrat,
S. Duthie,
N. Brockdorff,
M.G. Mattei,
M.A. Gavin,
N.A. Affara,
G.M. Brown,
E. Simpson
1998.
Characterization of genes encoding translation initiation factor eIF-2
 in mouse and human: Sex chromosome localization, escape from X-inactivation and evolution.
Hum. Mol. Genet.
7:
1725-1737[Abstract/Free Full Text]. -
Eicher, E.M.,
J.L. Southard,
C.R. Scriver, and
F.H. Glorieux.
1976.
Hypophosphatemia: Mouse model for human familial hyposphosphatemic (vitamin D-resistant) rickets.
Proc. Natl. Acad. Sci.
73:
4667-4671[Abstract/Free Full Text].
-
Eppig, J.T. and
M. Strivens.
1999.
Finding a mouse: The International Mouse Strain Resource (IMSR).
Trends Genet.
15:
81-82[CrossRef][Medline].
-
Erkman, L.,
R.J. McEvilly,
L. Luo,
A.K. Ryan,
F. Hooshmand,
S.M. O'Connell,
E.M. Keithley,
D.H. Rapaport,
A.F. Ryan, and
M.G. Rosenfeld.
1996.
Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development.
Nature
381:
603-606[CrossRef][Medline].
-
Eshkind, L.G. and
R.E. Leube.
1995.
Mice lacking synaptophysin reproduce and form typical synaptic vesicles.
Cell Tiss. Res.
3:
423-433.
-
Essers, J.,
R.W. Hendriks,
S.M.A. Swagemakers,
C. Troelstra,
J. de Wit,
D. Bootsma,
J.H.J. Hoeijmakers, and
R. Kanaar.
1997.
Disruption of mouse RAD54 reduces ionizing radiation resistance.
Cell
89:
195-204[CrossRef][Medline].
-
Favor, J. and
W. Pretsch.
1990.
Genetic localization and phenotypic expression of X-linked cataract (Xcat) in Mus musculus.
Genet. Res.
56:
157-162[Medline].
-
Fisher, E.M.C.
1997.
The contribution of the mouse to advances in human genetics.
Adv. Genet.
35:
155-205[Medline].
-
ForssPetter, S.,
H. Werner,
J. Berger,
H. Lassmann,
B. Molzer,
M.H. Schwab,
H. Bernheimer,
F. Zimmermann, and
K.A. Nave.
1997.
Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice.
J. Neurosci. Res.
50:
829-843[CrossRef][Medline].
-
Fransen, E.,
R. Dhooge,
G. van Camp,
M. Verhoye,
J. Sijbers,
E. Reyniers,
P. Soriano,
H. Kamiguchi,
R. Willemsen,
S.K.E. Koekkoek
1998.
L1 knockout mice show dilated ventricles, vernis hypoplasia and impaired exploration patterns.
Hum. Mol. Genet.
7:
999-1009[Abstract/Free Full Text].
-
Fujiwara, Y.,
C.P. Browne,
K. Cunniff,
S.C. Goff, and
S.H. Orkin.
1996.
Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1.
Proc. Natl. Acad. Sci.
93:
12355-12358[Abstract/Free Full Text].
-
Gan, L.,
M. Xiang,
L. Zhou,
D.S. Wagner,
W.H. Klein, and
J. Nathans.
1996.
POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells.
Proc. Natl. Acad. Sci.
93:
3920-3925[Abstract/Free Full Text].
-
Garber, E.D.
1952.
"Bent-tail", a dominant sex-linked mutation in the mouse.
Proc. Natl. Acad. Sci.
38:
8786-8789.
-
Gaspar, M.-L.,
T. Meo,
P. Bourgarel,
J.-L. Guenet, and
M. Tosi.
1991.
A single base deletion in the Tfm androgen receptor gene creates a short-lived messenger RNA that directs internal translation initiation.
Proc. Natl. Acad. Sci.
88:
8606-8610[Abstract/Free Full Text].
-
George, A.M.,
V. Reed,
P. Glenister,
Z. Tümer,
N. Horn,
J. Chelly,
A.P. Monaco, and
Y. Boyd.
1994.
Analysis of Mnk, the murine homologue of the locus for Menkes disease, in normal and mottled (Mo) mice.
Genomics
37:
96-104.
-
Gormally, E. and
Y. Boyd.
1998.
Faint lined (Fnl): A novel X-linked coat mutant in the mouse.
Genet. Res.
72:
211-216[CrossRef][Medline].
-
Greenwood, A.D.,
E.M. Southard-Smith,
A.T.J. Galecki, and
D.T. Burke.
1997.
Coordinate control and variation in X-linked gene expression among female mice.
Mamm. Genome
8:
818-822[CrossRef][Medline].
-
Griffiths, I.R.,
I. Scott,
M.C. McCulloch,
J.A. Barrie,
K. McPhilemy, and
B.M. Cattanach.
1990.
Rumpshaker mouse: A new X-linked mutation affecting myelination: Evidence for a defect in PLP expression.
J. Neurocytol.
19:
273-283[CrossRef][Medline].
-
Griffiths, I.R.,
A. Schneider,
J. Anderson, and
K.A. Knave.
1995.
Transgenic and natural mouse models of proteolipid (PLP)-related dysmyelination and demyelination.
Brain Pathol.
5:
275-281[Medline].
-
Griffiths, I.R.,
M. Klugmann,
T. Anderson,
C. Thomson,
D. Vouyiouklis, and
K.A. Nave.
1998.
Current concepts of PLP and its role in the nervous system.
Microscop. Res. Technique
41:
344-358.
-
Grimsby, J.,
M. Toth,
K. Chen,
T. Kumazawa,
L. Klaidman,
J.D. Adams,
F. Karoum,
J. Gal, and
J.C. Shih.
1997.
Increased stress response and -phenylethylamine in MAOB-deficient mice.
Nat. Genet.
17:
206-210[CrossRef][Medline].
-
Guenet, J.-L.,
C. Nagamine,
D. Simon-Chazettes,
X. Montagutelli, and
F. Bonhomme.
1990.
Hst-3: And X-linked hybrid sterility gene.
Genet. Res.
56:
163-165[Medline].
-
Hampton, L.L.,
E.E. Ladenheim,
M. Akeson,
J.M. Way,
H.C. Weber,
V.E. Sutliff,
R.T. Jensen,
L.J. Wine,
H. Arnheiter, and
J.F. Battey.
1998.
Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice.
Proc. Natl. Acad. Sci.
6:
3188-3192.
-
Happle, R.
1983.
Homologous genes for X-linked dominant chondrodysplasia punctata in man and mouse.
Hum. Genet.
63:
24-27[CrossRef][Medline].
-
Hein, L.,
G.S. Barsh,
R.E. Pratt,
V.J. Dzau, and
B.K. Kobilka.
1995.
Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice.
Nature
377:
744-747[CrossRef][Medline].
-
Heller, E. and
D.H. Pluznik.
1984.
Chromosomal assignment of two murine genes controlling susceptibility to spleen focus formation by Rauscher leukemia virus.
Exp. Hematol.
12:
645-649[Medline].
-
Hetherington, C.
1977.
Research News.
Mouse NewsLett.
56:
35.
-
Hooper, M.,
K. Hardy,
A. Handyside,
S. Hunter, and
M. Monk.
1987.
HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells.
Nature
326:
292-295[CrossRef][Medline].
-
Hunsicker, P.R.
1969.
Research News.
Mouse NewsLett.
40:
42.
-
Hunsicker, P.R.
1974.
New mutants: Eye-ear reduction Ie.
Mouse NewsLett.
50:
51-52.
-
Hunt, D.M.
1974.
Primary defect in copper transport underlies mottled mutants in the mouse.
Nature
249:
852-854[CrossRef][Medline].
-
Huq, A.H.M.M.,
R.S. Lovell,
C.N. Ou,
A.L. Beaudet, and
W.J. Craigen.
1997.
X-linked glycerol kinase deficiency in the mouse leads to growth retardation, altered fat metabolism, autonomous glucocorticoid secretion and neonatal death.
Hum. Mol. Genet.
6:
1803-1809[Abstract/Free Full Text].
-
Ichiki, T.,
P.A. Labosky,
C. Shiota,
S. Okuyama,
Y. Imagawa,
A. Fogo,
F. Niimura,
I. Ichikawa,
B.L.M. Hogan, and
T. Inagami.
1995.
Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor.
Nature
377:
748-750[CrossRef][Medline].
-
Janne, P.A.,
S.F. Suchy,
D. Bernard,
M. MacDonald,
J. Crawley,
A. Grinberg,
A. Wynshaw-Boris,
H. Westphal, and
R.L. Nussbaum.
1998.
Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.
J. Clin. Invest.
101:
2042-2053[Medline].
-
Justice, M.J.,
B. Zheng,
R.P. Woychik, and
A. Bradley.
1997.
Using targeted large deletions and high efficiency N-ethyl-N-nitrosourea mutagenesis for functional analyses of the mammalian genome.
Methods: Companion Methods Enzymol.
13:
423-436.
-
Kerner, J.D.,
M.W. Appleby,
R.N. Mohr,
S. Chien,
D.J. Rawlings,
C.R. Maliszewski,
O.N. Witte, and
R.M. Perlmutter.
1995.
Impaired expansion of mouse B cell progenitors lacking Btk.
Immunity
3:
301-312[CrossRef][Medline].
-
Khan, W.N.,
A. Nilsson,
E. Mizoguchi,
E. Castigli,
J. Forsell,
A.K. Bhan,
R. Geha,
P. Sideras, and
F.W. Alt.
1997.
Impaired B cell maturation in mice lacking Bruton's tyrosine kinase (Btk) and CD40.
Int. Immunol.
9:
395-405[Abstract/Free Full Text].
-
Kingston, P.J.,
C.E.M. Bannerman, and
R.M. Bannerman.
1978.
Iron deficiency anaemia in newborn sla mice: A genetic defect of placental iron transport.
Br. J. Haematol.
40:
265-276[Medline].
-
Klugman, M.,
M.H. Schwab,
A. Pulhofer,
A. Schneider,
F. Zimmerman,
I.R. Griffiths, and
K.A. Knave.
1997.
Assembly of CNS melin in the absence of proteolipid protein.
Neuron
18:
59-70[CrossRef][Medline].
-
Kuehn, M.R.,
A. Bradley,
E.J. Robertson, and
M.J. Evans.
1987.
A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice.
Nature
326:
295-298[CrossRef][Medline].
-
Lane, P.W. and
M.T. Davisson.
1990.
Patchy fur (Paf), a semidominant X-linked gene associated with a high level of X-Y nondisjunction in male mice.
J. Hered.
81:
43-50[Abstract/Free Full Text].
-
Larsen, M.M.
1964.
Research news: Greasy.
Mouse NewsLett.
30:
47.
-
Laval, S.H. and
Y. Boyd.
1993.
Partial inversion of gene order within an homologous segment on the X chromosome.
Mamm. Genome
4:
119-123[CrossRef][Medline].
-
Laverty, H.G. and
J.B. Wilson.
1998.
Murine CASK is disrupted in a sex-linked cleft palate mouse mutant.
Genomics
53:
29-41[CrossRef][Medline].
-
Leonard, W.J.,
E.W. Shores, and
P.E. Love.
1995.
Role of common cytokine receptor gamma chain in cytokine signaling and lymphoid development.
Immunol. Rev.
148:
97-114[CrossRef][Medline].
-
Li, M.,
J.A. Squire, and
R. Weksberg.
1998.
Overgrowth syndromes and genomic imprinting: From mouse to man.
Clin. Genet.
53:
165-170[Medline].
-
Liu, X.Y.,
A.W. Dangel,
R.I. Kelley,
W. Zheo,
P. Denny,
M. Botcherby,
B. Cattanach,
J. Peters,
P.R. Hunsicker,
A.-M. Mallon
1999.
The mouse bare patches and striated gene encodes a novel 3-hydroxysteroid dehydrogenase.
Nat. Genet.
22:
182-187[CrossRef][Medline].
-
Lorenz, B.,
F. Francis,
K. Gempel,
A. Boddrich,
M. Josten,
W. Schmahl,
J. Schmidt,
H. Lehrach,
T. Meitinger, and
T.M. Strom.
1999.
Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene.
Hum. Mol. Genet.
7:
541-547[Abstract/Free Full Text].
-
Lu, J.F.,
A.M. Lawler,
P.A. Watkins,
J.M. Powers,
A.B. Moser,
H.W. Moser, and
K.D. Smith.
1997.
A mouse model of X-linked adrenoleukodystrophy.
Proc. Natl. Acad. Sci.
94:
9366-9371[Abstract/Free Full Text].
-
Luoh, S.W.,
P.A. Bain,
R.D. Polakiewicz,
M.L. Goodheart,
H. Gardner,
R. Jaenisch, and
D.C. Page.
1997.
ZFX mutation results in small animal size and reduced germ cell number in male and female mice.
Development
124:
2275-2284[Abstract].
-
Lyon, M.F.
1999.
X-inactivation.
Curr. Biol.
9:
R235-R237[CrossRef][Medline].
-
Lyon, M.F.,
B.M. Cattanach, and
H.M. Charlton.
1981a.
Genes affecting sex differentiation in mammals.
In Mechanisms of sex differentiation in animals and man (ed. C.R. Austin and
R.G. Edwards), pp. 329-386. Academic Press, New York, NY.
-
Lyon, M.F.,
R.J.S. Phillips, and
G. Fisher.
1981b.
Use of an inversion to test for induced X-linked lethals in mice.
Mutat. Res.
92:
217-228.
-
Lyon, M.F.,
C.R. Scriver,
L.R.I. Baker,
H.S. Tenenhouse,
J. Kronick, and
S. Mandla.
1986.
The Gy mutation: Another cause of X-linked hypophosphatemia in mouse.
Proc. Natl. Acad. Sci.
43:
4899-4903.
-
Lyon, M.F.,
J. Peters,
P.H. Glenister,
S. Ball, and
E. Wright.
1990.
The scurfy mouse has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.
Proc. Natl. Acad. Sci.
87:
2433-2437[Abstract/Free Full Text].
-
Marra, M.,
L.-D. Hillier,
T. Kucaba,
M. Allen,
R. Barstead,
C. Beck,
A. Blistain,
M. Bonaldi,
Y. Bowers,
L. Bowles
1999.
An encylopedia of mouse genes.
Nat. Genet.
21:
191-194[CrossRef][Medline].
-
Marahens, Y.,
B. Panning,
J. Dausman,
W. Strauss, and
R. Jaenisch.
1997.
Xist-deficient mice are defective in dosage compensation but not spermatogenesis.
Genes & Dev.
11:
156-166[Abstract/Free Full Text].
-
Marsh, J.A.,
T.E. Wheat, and
E. Goldberg.
1977.
Temporal regulation of the immune response to LDH-C4 by an X-linked gene in C3H/HeJ and SJl/J mice.
J. Immunol.
118:
2293-2295[Abstract/Free Full Text].
-
McMahon, H.T.,
V.Y. Bolshakov,
R. Janz,
R.E. Hammer,
S.A. Siegelbaum, and
T.C. Sudhof.
1996.
Synaptophysin, a major synaptic vesicle protein is not essential for neurotransmitter release.
Proc. Natl. Acad. Sci.
10:
4760-4764.
-
Meier, H. and
A.D. MacPike.
1970.
A neurological mutation (msd) of the mouse causing a deficiency of myelin synthesis.
Exp. Brain Res.
10:
510-525.
-
Meyers, E.N.,
M. Lewandoski, and
G.R. Martin.
1998.
An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination.
Nat. Genet.
18:
136-141[CrossRef][Medline].
-
Miller, J.R.
1990.
X-linked traits: A catalog of loci in non-human mammals. Cambridge University Press, Cambridge, UK.
-
Minowa, O.,
K. Ikeda,
Y. Sugitani,
T. Oshima,
S. Nakai,
Y. Katori,
M. Suzuki,
M. Furukawa,
T. Kawase,
Y. Zheng
1999.
Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness.
Science
285:
1408-1411[Abstract/Free Full Text].
-
Morgenstern, D.E.,
M.A. Gifford,
L.L. Li,
C.M. Doerschuk, and
M.C. Dinauer.
1997.
Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defence and inflammatory response to Aspergillus fumigatus.
J. Exp. Med.
185:
207-218[Abstract/Free Full Text].
-
Mozes, E. and
S. Fuchs.
1974.
Linkage between iummune response potential to DNA and X chromosome.
Nature
249:
167-168[CrossRef][Medline].
-
Müller, U.
1999.
Ten years of gene targeting: Targeted mouse mutants, from vector design to phenotype analysis.
Mech. Dev.
82:
3-21[CrossRef][Medline].
-
Nehls, M.,
M. Messerle,
A. Sirulnik,
A.J. Smith, and
T. Boehm.
1994.
Two large insert vectors lambda PS and lambda Ko, facilitate rapid mapping and targeted disruption of mammalian genes.
BioTechniques
17:
770-775[Medline].
-
Nothnick, W.B.,
P. Soloway, and
T.E. Curry.
1997.
Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene.
Biol. Reprod.
56:
1181-1188[Abstract].
-
Ogura, H.,
S. Takada,
N. Mise,
M. Sugimoto,
S.-S. Tan, and
N. Takagi.
1998.
Translocation breakpoint possibly predisposes to nonrandom X-chromosome inactivation in mouse embryos bearing Searle's T(X;16)16H translocation.
Cytogenet. Cell Gen
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