Cloning and molecular characterization of telomerase reverse transcriptase (TERT) and telomere length analysis of Peromyscus leucopus.
Cloning and molecular characterization of telomerase reverse transcriptase (TERT) and telomere length analysis of Peromyscus leucopus.
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Peromyscus leucopus 端粒酶逆转录酶 (TERT) 的克隆和分子表征以及端粒长度分析。
DOI：
10.1016/j.gene.2015.05.013
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Young,NealS
中科院分区：
文献类型：
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作者：
Zhao,Xin;Ueda,Yasutaka;Kajigaya,Sachiko;Alaks,Glen;Desierto,MarieJ;Townsley,DanielleM;Dumitriu,Bogdan;Chen,Jichun;Lacy,RobertC;Young,NealS
端粒酶逆转录酶（TERT）是端粒酶复合体的催化亚基，在所有线性染色体动物中调节端粒酶活性以维持端粒长度。由于实验室小鼠的端粒比人类的端粒长，因此端粒研究的一个潜在替代动物模型是白底鼠（peromyscus leucopus， PL）小鼠，它的端粒长度接近人类的范围，并且有野生的对应物可供比较。我们报道了PL小鼠的全tertcoding序列（pTERT）用于端粒研究。与其他8种哺乳动物TERT的比较分析显示，pTERT蛋白与其他TERT相当同源，并保留了所有TERT特异性序列特征，但具有一些独特的特征。ptert与仓鼠tert的核苷酸和氨基酸序列同源性最高。与人不同但与MM小鼠相似的是，ptert在PL小鼠的各种成年体细胞组织中均有表达，其中睾丸中表达量最高。四种不同的圈养PL小鼠种群和野生捕获的PL小鼠均显示出组特异性的平均端粒长度，近交系和远交系小鼠的端粒长度分别最长和最短。ptert显示出相当数量的同义和非同义突变。克隆的pTERTproximal启动子区域在PL和MM小鼠和大鼠中具有同源性，但具有种特异性。从PL小鼠中，我们进一步克隆和鉴定了核糖体蛋白，大，P0 (pRPLP0)，作为各种检测的内部对照。Peromyscusmice已广泛用于各种研究，包括人类疾病，其中pTERTand prplp0将是有用的工具。
Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase complex that regulates telomerase activity to maintain telomere length for all animals with linear chromosomes. As theMus musculus(MM) laboratory mouse has very long telomeres compared to humans, a potential alternative animal model for telomere research is thePeromyscus leucopus(PL) mouse that has telomere lengths close to the human range and has the wild counterparts for comparison. We report the fullTERTcoding sequence (pTERT) from PL mice to use in the telomere research. Comparative analysis with eight other mammalian TERTs revealed a pTERT protein considerably homologous to other TERTs and preserved all TERT specific-sequence signatures, yet with some distinctive features. pTERTdisplayed the highest nucleotide and amino acid sequence homology with hamsterTERT. Unlike human but similar to MM mice, pTERTexpression was detected in various adult somatic tissues of PL mice, with the highest expression in testes. Four different captive stocks of PL mice and wild-captured PL mice each displayed group-specific average telomere lengths, with the longest and shortest telomeres in inbred and outbred stock mice, respectively. pTERTshowed considerable numbers of synonymous and nonsynonymous mutations. A pTERTproximal promoter region cloned was homologous among PL and MM mice and rat, but with species-specific features. From PL mice, we further cloned and characterized ribosomal protein, large, P0 (pRPLP0) to use as an internal control for various assays.Peromyscusmice have been extensively used for various studies, including human diseases, for which pTERTand pRPLP0would be useful tools.