Genetic mutation associated with meiotic metaphase-specific apoptosis in MRL/MpJ mice
Genetic mutation associated with meiotic metaphase-specific apoptosis in MRL/MpJ mice
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DOI：
10.1002/mrd.10208
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发表时间：
2003-02-01
影响因子：
2.5
通讯作者：
Kon, Y
中科院分区：
文献类型：
--
作者：
Namiki, Y;Endoh, D;Kon, Y
据报道，MRL/MpJ小鼠品系显示出几种独特的表型，包括快速伤口愈合，固有胶原蛋白疾病，耐热休克精子细胞和睾丸中期特异性凋亡（Msa）。在本研究中，我们通过对555个回交后代的染色体定位发现了与Msa相关的基因突变。在前200个雄性回交后代中，雌性F1（雌性C57BL/6 ×雄性MRL/MpJ）与雄性MRL/MpJ小鼠交配产生的异常变差精母细胞Sertoli细胞指数明显分为两组，表明Msa仅由一个基因引起。利用微卫星标记和单核苷酸多态性（SNP）对555个回交后代进行染色体定位，结果表明Msa定位在1号染色体的端粒区，并与外切酶1 （Exo1）和绒毛膜样（兔护蛋白2）（Chml/Rep2）基因显著相关。通过对几个近交系的核苷酸序列分析，发现Chml/Rep2基因不是Msa的候选基因。在菌株MRL/MpJ的Exo1基因上，但在其他菌株中没有，令人惊讶的是，通过逆转录-聚合酶链反应（RT-PCR）发现，截断形式（tr1-Exo1和tr2-Exo1）在所有被检查的组织中以及正常的Exo1中都表达。此外，外显子的截断形式被认为是通过第9外显子的选择性剪接转录的，可能是由于第8内含子分支位点的核苷酸替代。这些结果表明，MRL/MpJ小鼠睾丸减数分裂Msa是由Exo1基因不完全选择性剪接引起的一种独特表型。
It has been reported that the MRL/MpJ mouse strain shows several unique phenotypes, including rapid wound healing, inherent collagen disease, heat shock-resistant spermatocytes, and metaphase-specific apoptosis (Msa) in the testis. In the present study, we found the genetic mutation associated with Msa by chromosomal mapping with 555 backcross progeny. The Sertoli cell index of abnormal metaphasic spermatocytes was clearly divided into two groups in the first 200 male backcross progeny, which were created by mating female F1 (female C57BL/6 x male MRL/MpJ) with male MRL/MpJ mice, indicating that Msa was caused by only one gene. The result of chromosomal mapping throughout the 555 backcross progeny by using microsatellite markers and single nucleotide polymorphism (SNP) revealed that Msa was mapped on the telomeric region of chromosome 1 and was significantly linked with exonuclease 1 (Exo1) and choroideremia-like (rab escort protein 2) (Chml/Rep2) genes. It was found that the Chml/Rep2 gene was not a candidate for Msa by means of the nucleotide sequences of several inbred strains. On the Exo1 gene in strain MRL/MpJ, but not in other strains, it was surprisingly noted that the truncated forms (tr1-Exo1 and tr2-Exo1) were expressed in all tissues examined as well as normal Exo1 by reverse transcriptase-polymerase chain reaction (RT-PCR). Additionally, the truncated forms of the Exo1 gene were suggested to be transcribed by alternative splicing of the 9th exon, possibly resulting from nucleotide substitution of the branch site existing in the 8th intron. These results suggested that the testicular meiotic Msa in MRL/MpJ mice was a unique phenotype caused by incomplete alternative splicing of the Exo1 gene.