LETTER
Vestibular Dysfunction in the Epistatic circler Mouse Is Caused by Phenotypic Interaction of One Recessive Gene and Three Modifier Genes

¹ Department of Medical Genetics, University of Antwerp, B-2610 Antwerp, Belgium; ² Laboratory of Cell Biology and Histology, University of Antwerp, B-2020 Antwerp, Belgium; ³ Department of Otolaryngology, University of Antwerp, B-2610 Antwerp, Belgium; ⁴ Department of Anatomy, Neuroscience Institute, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands

Vestibular dysfunction is a frequent clinical problem, leading to dizziness and imbalance. Genes play an important role in its etiology, but the genetics are complex and poorly understood. In this study we have analyzed the complex inheritance pattern in the Epistatic circler mouse, which shows circling behavior indicative of vestibular dysfunction in the mouse. This phenotype exists in a proportion of the F2-generation from an intercross between C57L/J and SWR/J mouse strains. Genetic investigation indicates that the circling behavior is caused by a major recessively inherited gene derived from the SWR/J strain (the Ecs-gene) in combination with at least three different modifier genes derived from C57L/J (the Ecl-genes). Genetic mapping made it possible to localize the Ecs-gene to chromosome 14 and the Ecl-genes to chromosome 3, 4, and 13. This study illustrates the feasibility of identifying genes for multifactorial traits in mice.