Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse
Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse
复制标题
DOI：
10.1073/pnas.95.24.14361
复制
发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Moreadith, RW
中科院分区：
文献类型：
--
作者：
Watson, ML;Zinn, AR;Moreadith, RW
在减数分裂的I前期早期，小精子或更多的常染色体隐性突变导致精子发生停止。morc突变是在酪氨酸酶cDNA转基因小鼠株的发育过程中自发产生的。More -/-雄性不育且睾丸质量严重减少，而-/-雌性正常，表明More基因在雄性配子发生过程中起特殊作用。对突触复合抗原的免疫荧光显示-/-雄性生殖细胞进入减数分裂，但不能超过zygotene或lepptotene期。细胞凋亡实验显示-/-小鼠睾丸中有大量细胞发生凋亡。在突变动物中没有观察到其他异常表型，除了视网膜中转基因表达引起的眼睛色素沉着。精子发生在阳性/阴性男性中是正常的，尽管在生殖细胞中有显著的转基因表达。对-/-动物的基因组分析表明存在与转基因相邻的缺失。鉴定被转基因插入灭活的基因可能为哺乳动物生殖细胞发育和减数分裂提供一条新的生化途径。
The microrchidia, or more, autosomal recessive mutation results in the arrest of spermatogenesis early in prophase I of meiosis. The morc mutation arose spontaneously during the development of a mouse strain transgenic for a tyrosinase cDNA construct. More -/- males are infertile and have grossly reduced testicular mass, whereas -/- females are normal, indicating that the More gene acts specifically during male gametogenesis. Immunofluorescence to synaptonemal complex antigens demonstrated that -/- male germ cells enter meiosis but fail to progress beyond zygotene or leptotene stage. An apoptosis assay revealed massive numbers of cells undergoing apoptosis in testes of -/- mice. No other abnormal phenotype was observed in mutant animals, with the exception of eye pigmentation caused by transgene expression in the retina. Spermatogenesis is normal in +/- males, despite significant transgene expression in germ cells. Genomic analysis of -/- animals indicates the presence of a deletion adjacent to the transgene. Identification of the gene inactivated by the transgene insertion may define a novel biochemical pathway involved in mammalian germ cell development and meiosis.