New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis
New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis
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DOI：
10.1093/hmg/8.7.1201
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发表时间：
1999-07-01
影响因子：
3.5
通讯作者：
Zinn, AR
中科院分区：
文献类型：
--
作者：
Inoue, N;Hess, KD;Zinn, AR
哺乳动物精子发生是一个复杂的发育过程，对小鼠突变的分析为完成这一过程提供了所需的生化途径。我们以前描述了常染色体隐性遗传的小鼠MORC(TGN(Tyr)1AZ)突变，这是一种偶然的转基因插入突变，会导致精子发生在减数分裂前期I的粗线期之前停止。现在我们报告了MORC(TGN(Tyr)1AZ)突变所破坏的更多基因的分子特征和位置克隆。该基因编码108 kDa的蛋白质，在雄性生殖细胞中特异表达，转基因整合在MORC的第一内含子中，伴随着约13kb的基因组序列的基因内缺失，去除外显子2-4并取消野生型转录本的表达。对MORC蛋白序列的分析揭示了可能的核定位信号，预测的两个卷曲结构基序，以及与GHL(GyraseB，Hsp90，MutL)ATPase的有限同源性，在COS7细胞中表达的表位标记的MORC蛋白定位于细胞核。我们还克隆了人类MORC同源基因，并表明它也是睾丸特异的，但密切相关的人类基因在多个体细胞组织中转录。斑马鱼、线虫、黏菌和植物中也存在同源蛋白质。因此，克隆MORE定义了一个新的基因家族，其成员可能在多细胞生物体的减数分裂和有丝分裂细胞中发挥重要的生物学功能。
Mammalian spermatogenesis is a complex developmental process, The analysis of mouse mutations has provided insight into biochemical pathways required for completion of this process. We previously described the autosomal recessive mouse morc(TgN(Tyr)1Az) (microrchidia) mutation, a serendipitous transgenic insertional mutation which causes arrest of spermatogenesis prior to the pachytene stage of meiosis prophase I. We now report the molecular characterization of the more locus and positional cloning of a gene disrupted by the morc(TgN(Tyr)1Az) mutation. This gene, which we term Morc, encodes a 108 kDa protein expressed specifically in male germ cells, The transgene integrated within the first intron of Morc and was accompanied by an intragenic deletion of similar to 13 kb of genomic sequences, removing exons 2-4 and abrogating expression of the wild-type transcript. Analysis of the MORC protein sequence revealed putative nuclear localization signals, two predicted coiled-coil structural motifs and limited homology to GHL (GyraseB, Hsp90, MutL) ATPase, Epitope-tagged MORC protein expressed in COS7 cells localized to the nucleus. We also cloned the human MORC homolog and show that it too is testis-specific, but closely related human genes are transcribed in multiple somatic tissues. Homologous proteins are also present in zebrafish, nematodes, slime mold and plants. Thus, cloning of More defines a novel gene family whose members are likely to serve important biological functions in both meiotic and mitotic cells of multicellular organisms.