THE MOUSE PAX2(1NEU) MUTATION IS IDENTICAL TO A HUMAN PAX2 MUTATION IN A FAMILY WITH RENAL-COLOBOMA SYNDROME AND RESULTS IN DEVELOPMENTAL DEFECTS OF THE BRAIN, EAR, EYE, AND KIDNEY

We describe a new mouse frameshift mutation (Pax2(1Neu)) with a 1-bp i nsertion in the Pax2 gene, This mutation is identical to a previously described mutation in a human family with renal-coloboma syndrome [San yanusin, P., McNoe, L. A., Sullivan, M. J., Weaver, R. G. & Eccles, M. R. (1995) Hum. Mol. Genet. 4, 2183-2184], Heterozygous mutant mice ex hibit defects in the kidney, the optic nerve, and retinal layer of the eye, and in homozygous mutant embryos, development of the optic nerve , metanephric kidney, and ventral regions of the inner ear is severely affected, In addition, we observe a deletion of the cerebellum and th e posterior mesencephalon in homozygous mutant embryos demonstrating t hat, in contrast to mutations in Pax5, which is also expressed early i n the mid-hindbrain region, loss of Pax2 gene function alone results i n the early loss of the mid-hindbrain region, The mid-hindbrain phenot ype is similar to Wnt1 and En1 mutant phenotypes, suggesting the conse rvation of gene regulatory networks between vertebrates and Drosophila .