Miyazaki Takehiro, Fukui Manami, Inagaki Emi, Miki Kenji, Takabayashi Shuji, Katoh Hideki, Ohira Yukio, Noguchi Motoko, Tokumoto Toshinobu
1 Integrated Bioscience Section, Graduate School of Science and Technology, National University Corporation Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8529, Japan.
2 Department of Biological Science, Faculty of Science, National University Corporation Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8529, Japan.
Zoolog Sci. 2018 Apr;35(2):172-178. doi: 10.2108/zs170176.
Experimental testicular teratomas (ETTs) can be induced in 129/Sv mouse by E12.5 fetal testes transplant into adult testes. Previously, we conducted linkage analysis to explore candidate genes possibly involved in ETT development using F2 intercross fetuses derived from F1[LTXBJ × 129/Sv- + /Ter (+ /+)] hybrids. By linkage analysis on Chr 18 and Chr 19, we identified the genomic locus for experimental testicular teratoma 1 (ett1) on Chr 18. In the present study, we conducted additional mapping and linkage analysis on teratoma susceptibility and genome composition on Chr 1-17. The results revealed two new candidate loci, experimental testicular teratoma 2 (ett2) and experimental testicular teratoma 3 (ett3), on Chr 3 and 7. Interestingly, the rates of ETT generation were increased in the case of ett2 and ett3 regions replaced with LTXBJ strain. To determine whether a polymorphic gene was present, we performed exome analysis of 129/Sv- + /Ter (+ /+) and LTXBJ. This revealed the presence of SNPs in all three loci, ett1 to ett3. ett1 contains polymorphic Mc4r; ett2 contains polymorphic Polr3c, Cd160, and Pdzk1; and ett3 contains polymorphic Prmt3. We found additional loci responsible for ETT formation, namely, ett2 and ett3, and identified candidate genes in these regions by exome analysis.
通过将E12.5期胎儿睾丸移植到成年睾丸中，可在129/Sv小鼠中诱导出实验性睾丸畸胎瘤（ETT）。此前，我们利用来自F1[LTXBJ×129/Sv- + /Ter（+ /+）]杂种的F2代杂交胎儿进行连锁分析，以探索可能参与ETT发育的候选基因。通过对18号和19号染色体的连锁分析，我们在18号染色体上确定了实验性睾丸畸胎瘤1（ett1）的基因组位点。在本研究中，我们对1-17号染色体上的畸胎瘤易感性和基因组组成进行了额外的定位和连锁分析。结果在3号和7号染色体上发现了两个新的候选位点，即实验性睾丸畸胎瘤2（ett2）和实验性睾丸畸胎瘤3（ett3）。有趣的是，用LTXBJ品系替换ett2和ett3区域时，ETT生成率增加。为了确定是否存在多态性基因，我们对129/Sv- + /Ter（+ /+）和LTXBJ进行了外显子组分析。这揭示了在所有三个位点ett1至ett3中均存在单核苷酸多态性（SNP）。ett1包含多态性的Mc4r；ett2包含多态性的Polr3c、Cd160和Pdzk1；ett3包含多态性的Prmt3。我们发现了负责ETT形成的其他位点，即ett2和ett3，并通过外显子组分析确定了这些区域中的候选基因。
