In Drosophila, mutations in the gene eyes absent (eya) lead to severe defects in eye development. The functions of its mammalian orthologs Eya1-4 are only partially understood so far. In humans EYA1 haploinsufficiency is responsible for branchio-otorenal (BOR) syndrome or branchio-oto (BO) syndrome. BOR is an autosomal dominant disorder characterized by branchial cysts, ear malformations, hearing loss and renal abnormalities.
To better understand the function of the Eya genes in mammals, the phenotype of young adult Eya3 knockout mouse mutants was systematically analyzed within the German Mouse Clinic.
Previous analysis of expression patterns of Eya3 by in-situ hybridizations and b-Gal-staining of Eya3 mutant mice showed abundant expression of the gene throughout development, e.g. in brain, eyes, heart, somites and limbs suggesting pleiotropic effects of the mutated gene. Similar expression has been found in zebrafish embryos while the expression pattern in Xenopus embryos differs significantly.
Hence it might be possible that the Eya3 gene has different functions in different vertebrate species (mouse, human, fish and frog).
Phenotyping of Eya3 mutant mice in the German Mouse Clinic demonstrated a broad spectrum of physiological changes. The mutants showed decreased bone mineral content and shorter body length. In the lung, the tidal volume at rest was decreased, and the electrocardiography showed variations from the healthy pattern. Behavioral analysis of the mutants demonstrated that mutant mice are sligthly more curious but move less than their wild-type littermates. No obvious defects were found in the eyes, ears and kidneys of Eya3 mutant mice compared to the situation in humans with only one functioning copy of the EYA1 gene. All the diverse variations were found in young mutant mice. It might be possible that the phenotype becomes stronger when the mice become older.
Pleiotropic effects in Eya3 knockout mice“, Söker et al, BMC 2008, 8:118
For further information pleas contact
Prof. Dr. Jochen Graw
Phone: +49 (0)89 3187 2610