The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Biol Reprod. 2012 Feb 29;86(2):45. doi: 10.1095/biolreprod.111.095752. Print 2012 Feb.
The N-ethyl-N-nitrosourea-induced repro42 mutation, identified by a forward genetics strategy, causes both male and female infertility, with no other apparent phenotypes. Positional cloning led to the discovery of a nonsense mutation in Spata22, a hitherto uncharacterized gene conserved among bony vertebrates. Expression of both transcript and protein is restricted predominantly to germ cells of both sexes. Germ cells of repro42 mutant mice express Spata22 transcript, but not SPATA22 protein. Gametogenesis is profoundly affected by the mutation, and germ cells in repro42 mutant mice do not progress beyond early meiotic prophase, with subsequent germ cell loss in both males and females. The Spata22 gene is essential for one or more key events of early meiotic prophase, as homologous chromosomes of mutant germ cells do not achieve normal synapsis or repair meiotic DNA double-strand breaks. The repro42 mutation thus identifies a novel mammalian germ cell-specific gene required for meiotic progression.
N-乙基-N-亚硝脲诱导的 repro42 突变是通过正向遗传学策略鉴定的，它导致雄性和雌性不育，没有其他明显的表型。定位克隆导致了 Spata22 中的无义突变的发现，Spata22 是一个在硬骨鱼类中保守的、迄今为止尚未被描述的基因。转录本和蛋白的表达主要局限于两性生殖细胞。repro42 突变小鼠的生殖细胞表达 Spata22 转录本，但不表达 SPATA22 蛋白。生殖细胞发生受到突变的严重影响，repro42 突变小鼠的生殖细胞不能进入早期减数分裂前期，随后雄性和雌性生殖细胞都丢失。Spata22 基因对于早期减数分裂前期的一个或多个关键事件是必需的，因为突变生殖细胞的同源染色体不能实现正常的联会或修复减数分裂 DNA 双链断裂。因此，repro42 突变鉴定了一个新的哺乳动物生殖细胞特异性基因，该基因对于减数分裂进展是必需的。
