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。端粒长度因物种而异，甚至在小鼠品系中也是如此。本研究对新近建立的9个野生自交系小鼠的端粒长度多态性进行了筛选，发现KJR/Ms （KJR）小鼠端粒极短（约5 kb）。为了分析KJR小鼠短端粒表型的遗传位点，我们将KJR小鼠与C57BL/6J （B6J）小鼠进行杂交，C57BL/6J是具有长端粒（bbb40 kb）的标准实验室菌株。F_1小鼠端粒呈现双峰信号，表明B6J小鼠端粒较长，KJR小鼠端粒较短。与KJR亲本相比，B6J等位基因的端粒延长较短，说明KJR的表型是隐性的。KJR小鼠回交后代端粒长度增加，说明B6J等位基因的多个位点参与了KJR小鼠短端粒的延长。定量性状位点（QTL）分析显示，KJR小鼠短端粒贡献基因位点定位在13号染色体和3号染色体上。有趣的是，这两个基因座都包含端粒酶的两个核心成分（mTert和mTerc），这表明KJR小鼠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.