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.

Hematopoietic Aging Biomarkers in Peromyscus leucopus Mice

“…Despite shared features of appearance, PL mice differ drastically from MM mice in their higher physical agility [ 17 ], longer lifespan [ 4 ], and shorter telomeres [ 7 ]. PL mice belong to Genus Peromyscus of Subfamily Sigmodontinae while MM mice belong to Genus Mus of Subfamily Murinae in the taxonomic hierarchy, which means that these two species have been separated from each other for millions of years.…”

“…musculus (MM) [ 2 – 5 ]. Relative to MM mice, PL mice have fewer platelets and more monocytes [ 6 ] and their peripheral blood mononuclear cells have drastically shorter telomeres [ 7 ]. The characteristic short telomere and long lifespan in PL mice provide an interesting combination that favors the utility of PL mice as a potential model for aging studies.…”