Male-to-female sex reversal in M33 mutant mice
Male-to-female sex reversal in M33 mutant mice
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DOI：
10.1038/31482
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发表时间：
1998-06-18
期刊：
影响因子：
64.8
通讯作者：
Higashinakagawa, T
中科院分区：
文献类型：
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作者：
Katoh-Fukui, Y;Tsuchiya, R;Higashinakagawa, T
果蝇的多梳基因通过介导高阶染色质结构的变化来维持同质异体和其他发育调节基因的抑制状态（1-4）（5-7）。Polycomb的小鼠同源基因M33通过其色域的结构相似性被分离出来(8)。M33的第5外显子包含果蝇和爪蟾共有的同源区域（8,9）。在果蝇中，它的缺失导致Polycomb功能的丧失（10）。在这里，我们通过在小鼠M33的第五个外显子中插入一个poly(a)捕获型neo(r)靶向载体来破坏M33。超过一半的M33(cterm)/M33（cterm）突变小鼠在断奶前死亡，幸存者表现出雄性向雌性的性别逆转。XX和XY M33(cterm)/M33（cterm）胚胎生殖脊的形成均受到阻碍。性腺生长缺陷在y染色体特异性Sry基因表达前后出现（11），提示M33缺乏可能通过干扰Sry上游的步骤而导致性别逆转。M33(cterm)\M33（cterm）小鼠可能是一个有价值的模型，用于测试关于性别决定的对立观点。
Polycomb genes in Drosophila maintain the repressed state of homeotic and other developmentally regulated genes(1-4) by mediating changes in higher-order chromatin structure(5-7). M33, a mouse homologue of Polycomb, was isolated by means of the structural similarity of its chromodomain(8). The fifth exon of M33 contains a region of homology shared by Drosophila and Xenopus(8,9). In Drosophila, its deletion results in the loss of Polycomb function(10). Here we have disrupted M33 in mice by inserting a poly(A) capture-type neo(r) targeting vector into its fifth exon. More than half of the resultant M33(cterm)/M33(cterm) mutant mice died before weaning, and survivors showed male-to-female sex reversal. Formation of genital ridges was retarded in both XX and XY M33(cterm)/M33(cterm) embryos. Gonadal growth defects appeared near the time of expression of the Y-chromosome-specific Sry gene(11), suggesting that M33 deficiency may cause sex reversal by interfering with steps upstream of Sry. M33(cterm)\M33(cterm) mice may be a valuable model in which to test opposing views regarding sex determination.