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HP1γ function is required for male germ cell survival and spermatogenesis

机译:HP1γ功能是雄性生殖细胞存活和生精所必需的

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Background HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1α, HP1β and HP1γ, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1γ using a gene-targeted mouse. Results While targeting the Cbx3 gene (encoding the HP1γ protein) with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo), which resulted in much reduced (barely detectable) levels of HP1γ protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo) are rare, with only 1% of Cbx3hypo/hypo animals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype). The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p) in Cbx3hypo/hypo testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in Cbx3hypo/hypo germ cells. Conclusions The Cbx3 gene product (the HP1γ protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The Cbx3hypo/hypo spermatogenesis defect is similar to that found in Miwi2 and Dnmt3L mutants. The Cbx3 gene-targeted mice generated in this study provide an appropriate model for the study of HP1γ in transposon silencing and parental imprinting.
机译:背景HP1蛋白是真核组成型异染色质的保守成分。在哺乳动物中,有三种编码HP1样蛋白的基因,分别称为HP1α,HP1β和HP1γ,它们具有高度的同源性。本文据我们所知首次描述了以基因为靶点的HP1γ的生理功能。老鼠。结果用条件靶向载体靶向Cbx3基因(编码HP1γ蛋白)时,我们产生了一个亚型等位基因(Cbx3 hypo ),导致HP1γ蛋白水平大大降低(几乎检测不到)。亚型等位基因(Cbx3 hypo / hypo )的纯合子很少见,只有1%的Cbx3 hypo / hypo 动物成年。成年男性表现出严重的性腺机能减退,这与生殖细胞的丧失有关,一些生精小管仅保留支持性支持细胞(仅支持Sertoli的表型)。 Cbx3 hypo / hypo 睾丸中L1 ORF1蛋白(ORF1p)阳性的曲细精管百分比高于野生型睾丸,表明L1逆转座子沉默被逆转,导致异位表达Cbx3 hypo / hypo 生殖细胞中ORF1p的表达。结论Cbx3基因产物(HP1γ蛋白)在精子发生过程中具有非冗余功能,其他两种HP1亚型无法弥补这一功能。 Cbx3 hypo / hypo 精子发生缺陷类似于在Miwi2和Dnmt3L突变体中发现的缺陷。在这项研究中生成的针对Cbx3基因的小鼠为转座子沉默和亲子印迹研究HP1γ提供了合适的模型。

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