Mice mutant in the DM domain gene Dmrt4 are viable and fertile but have polyovular follicles

Mice mutant in the DM domain gene Dmrt4 are viable and fertile but have polyovular follicles
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DOI:
10.1128/mcb.00959-06
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发表时间:
2006-12-01
影响因子:
5.3
通讯作者:
Zarkower, David
Zarkower, David
中科院分区:
生物学2区
文献类型:
--
作者:
Balciuniene, Jorune;Bardwell, Vivian J.;Zarkower, David

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含有DM结构域(锌指样DNA结合基序)的蛋白质与多种后生动物的性别分化有关。在7个哺乳动物DM结构域基因中,只有Dmrt 1和Dmrt 2已被功能分析。在这里,我们报告了小鼠中Dmrt4(也称为DmrtA1)的表达分析和靶向破坏。Dmrt4在胚胎和出生后发育过程中广泛表达。然而,我们发现Dmrt4中假定无效突变的纯合子小鼠发育基本正常,在两性中经历完全的性分化,并且是可生育的。我们在Dmrt4突变小鼠中观察到两种潜在的突变表型。首先,大多数突变雌性的卵巢具有多胚珠卵泡,表明在卵泡发生中的作用。第二,25%的突变体男性一贯表现出交配行为对其他男性。我们还测试了Dmrt4和其他两个性腺表达的DM结构域基因,Dmrt1和Dmrt7之间的潜在冗余。我们观察到没有增强的性腺表型的双突变体,这表明这些基因的功能独立的性腺发育。
Proteins containing the DM domain, a zinc finger-like DNA binding motif, have been implicated in sexual differentiation in diverse metazoan organisms. Of seven mammalian DM domain genes, only Dmrt1 and Dmrt2 have been functionally analyzed. Here, we report expression analysis and targeted disruption of Dmrt4 (also called DmrtA1) in the mouse. Dmrt4 is widely expressed during embryonic and postnatal development. However, we find that mice homozygous for a putative null mutation in Dmrt4 develop essentially normally, undergo full sexual differentiation in both sexes, and are fertile. We observed two potential mutant phenotypes in Dmrt4 mutant mice. First, ovaries of most mutant females have polyovular follicles, suggesting a role in folliculogenesis. Second, 25% of mutant males consistently exhibited copulatory behavior toward other males. We also tested potential redundancy between Dmrt4 and two other gonadally expressed DM domain genes, Dmrt1 and Dmrt7. We observed no enhancement of gonadal phenotypes in the double mutants, suggesting that these genes function independently in gonadal development.