BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin
BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin
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DOI：
10.1038/11896
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发表时间：
1999-08-01
期刊：
影响因子：
30.8
通讯作者：
Heintz, N
中科院分区：
文献类型：
--
作者：
Yang, XW;Wynder, C;Heintz, N
小鼠的遗传分析通常采用两种策略：表型筛选自发或诱导突变，以及利用同源重组或基因捕获进行基因分型以产生缺失或插入突变。在这里，我们在转基因小鼠中使用细菌人工染色体(BAC)介导的基因剂量分析来揭示传统功能缺失突变不明显的新的遗传功能。我们证明了锌指转录因子Zipro1(以前的Ru49和Zfp38)在发育中的小脑颗粒细胞前体细胞增殖中的作用，并证明了这一过程对小脑形态发生的最后阶段的贡献。我们还发现，ZiproI在皮肤中表达，增加Zipro1的剂量会导致脱发表型，并伴随着上皮细胞增殖增加和毛囊发育异常。
Geneticanalysis in mice has most commonly employed two general strategies: phenotypic screens for spontaneous or induced mutations and genotypic analysis using homologous recombination or gene trapping to produce deletion or insertion mutants. Here we use bacterial artificial chromosome (BAC)-mediated gene-dosage analysis in transgenic mice to reveal novel genetic functions that are not evident from conventional loss-of-function mutations. We demonstrate a role for the zinc-finger transcription factor Zipro1 (formerly Ru49 and Zfp38) in the proliferation of granule cell precursors in the developing cerebellum, and document the contribution of this process to the final stages of cerebellar morphogenesis. We also show that Zipro I is expressed in skin, and increased Zipro1 dosage results in a hair-loss phenotype associated with increased epithelial cell proliferation and abnormal hair follicle development.