Quantitative trait loci mapping for short telomeres in wild-derived mice

端粒是真核生物染色体末端的核蛋白结构。端粒长度在物种之间变化，甚至在小鼠品系中也是如此。在这项研究中，我们筛选的端粒长度多态性的9个野生衍生的近交系，最近建立的小鼠股票，并发现KJR/MS（KJR）小鼠具有极短的端粒（约5 kb）。为了分析KJR小鼠中促成短端粒表型的遗传基因座，我们将KJR小鼠与具有长端粒（>40 kb）的标准实验室品系C57 BL/6 J（B6 J）小鼠杂交。F_1代小鼠端粒信号呈双峰型，表明B6 J小鼠遗传了较长的端粒，而KJR小鼠遗传了较短的端粒。与KJR亲本相比，B6 J等位基因延长了较短的端粒，表明KJR的表型为隐性。与KJR小鼠回交后代的端粒长度呈倍数增长，表明B6 J等位基因的多个位点有助于KJR小鼠短端粒的延长。数量性状基因座（QTL）分析表明，KJR小鼠短端粒的贡献者的遗传位点定位在染色体13和3。有趣的是，这两个位点都包含端粒酶的两个核心组分（mTert和mTerc），表明KJR小鼠中的端粒酶可能影响其短端粒表型。

Telomere is the nucleoprotein structure at the end of eukaryotic chromosome. Telomere length varies among species, and even in strains in mice. In this study, we screened the telomere length polymorphism among nine wild-derived inbred strains that are recently established mice stocks, and found that KJR/Ms (KJR) mice have extreme short telomeres (about 5 kb). To analyze the genetic loci contributing short telomere phenotype in KJR mice, we crossed KJR mice and C57BL/6J (B6J) mice, standard laboratory strain that possess long telomeres (>40 kb). F_1 mice showed bimodal telomere signals, indicating that longer set of telomeres is inherited from B6J and shorter one is from KJR mice. The shorter set of telomeres was elongated by B6J allele compared with the one of KJR parent, indicating that the phenotype of KJR is recessive. Backcross progenies to KJR mice showed the multiple length of telomeres, indicating that multiple loci of B6J allele contribute to elongate the short telomeres of KJR mice. Quantitative trait loci (QTL) analysis revealed that the genetic loci for contributors to short telomeres in KJR mice were mapped on chromosome 13 and 3. Interestingly, both loci include two core components of telomerase (mTert and mTerc), indicating that the telomerase in KJR mice may affect their short telomere phenotype.