Dandy-Walker malformation (DWM; OMIM #220200) is a common but poorly understood congenital cerebellar malformation in humans. Through physical mapping of 3q2 interstitial deletions in several individuals with DWM, we defined the first critical region associated with DWM, encompassing two adjacent Zinc finger in cerebellum genes, ZIC1 and ZIC4. Mice with a heterozygous deletion of these two linked genes have a phenotype that closely resembles DWM, providing a mouse model for this malformation.
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We thank the affected individuals and their families for their participation, P. Soriano for providing the pPGKneo DTA vector and E. McNally and C. Roe for discussions and reading the manuscript. This work was supported by a Ragins-Goldsmith Fellowship and the Medical Scientist Training grant (to I.G.), a grant from the Brain Research Foundation of Chicago (to K.J.M.) and grants from the National Institute of Health (to K.J.M. and W.B.D.).