BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin

Geneticanalysis in mice has most commonly employed two general strategies: phenotypic screens for spontaneous or induced mutations and genotypic analy sis using homologous recombination or gene trapping to produce deletion or insertion mutants. Here we use bacterial artificial chromosome (BAC)-mediat ed gene-dosage analysis in transgenic mice to reveal novel genetic function s that are not evident from conventional loss-of-function mutations. We dem onstrate a role for the zinc-finger transcription factor Zipro1 (formerly R u49 and Zfp38) in the proliferation of granule cell precursors in the devel oping cerebellum, and document the contribution of this process to the fina l stages of cerebellar morphogenesis. We also show that Zipro I is expresse d in skin, and increased Zipro1 dosage results in a hair-loss phenotype ass ociated with increased epithelial cell proliferation and abnormal hair foll icle development.