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Background  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 and no mouse model exists for  Eya3 . Therefore, we characterized the phenotype of a new  Eya3  knockout mouse mutant.    Results  Expression analysis of  Eya3  by  in-situ  hybridizations and β-Gal-staining of  Eya3  mutant mice revealed abundant expression of the gene throughout development, e.g. in brain, eyes, heart, somites and limbs suggesting pleiotropic effects of the mutated gene. A similar complex expression pattern was observed also in zebrafish embryos.  The phenotype of young adult  Eya3  mouse mutants was systematically analyzed within the German Mouse Clinic. There was no obvious defect in the eyes, ears and kidneys of  Eya3  mutant mice. Homozygous mutants displayed decreased bone mineral content and shorter body length. In the lung, the tidal volume at rest was decreased, and electrocardiography showed increased JT- and PQ intervals as well as decreased QRS amplitude. Behavioral analysis of the mutants demonstrated a mild increase in exploratory behavior, but decreased locomotor activity and reduced muscle strength. Analysis of differential gene expression revealed 110 regulated genes in heart and brain. Using real-time PCR, we confirmed  Nup155  being down regulated in both organs.    Conclusion  The loss of  Eya3  in the mouse has no apparent effect on eye development. The wide-spread expression of  Eya3  in mouse and zebrafish embryos is in contrast to the restricted expression pattern in  Xenopus  embryos. The loss of  Eya3  in mice leads to a broad spectrum of minor physiological changes. Among them, the mutant mice move less than the wild-type mice and, together with the effects on respiratory, muscle and heart function, the mutation might lead to more severe effects when the mice become older. Therefore, future investigations of  Eya3  function should focus on aging mice.

Pleiotropic effects in Eya3knockout mice