title: Cloning and molecular characterization of telomerase reverse transcriptase (TERT) and telomere length analysis of Peromyscus leucopus.
abstract: 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 the Mus musculus (MM) laboratory mouse has very long telomeres compared to humans, a potential alternative animal model for telomere research is the Peromyscus leucopus (PL) mouse that has telomere lengths close to the human range and has the wild counterparts for comparison. We report the full TERT coding 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. pTERT displayed the highest nucleotide and amino acid sequence homology with hamster TERT. Unlike human but similar to MM mice, pTERT expression 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. pTERT showed considerable numbers of synonymous and nonsynonymous mutations. A pTERT proximal 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. Peromyscus mice have been extensively used for various studies, including human diseases, for which pTERT and pRPLP0 would be useful tools.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: zhaox10@nhlbi.nih.gov.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kajigaya
authors.affiliation: Department of Conservation Science, Chicago Zoological Society, Brookfield, IL, USA.
authors.forename: Glen
authors.initials: G
authors.lastname: Alaks
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Desierto
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Townsley
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Dumitriu
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Conservation Science, Chicago Zoological Society, Brookfield, IL, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Lacy
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D015870:Gene Expression; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010542:Peromyscus / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019098:Telomerase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis; D013737:Testis / Q000201:enzymology
chemical_list: D019098:Telomerase
keywords: Cloning; Large; P0 (RPLP0); Ribosomal protein; TERT mutation