Mus musculus and Mus spretus homologues of the human telomere-associated protein TIN2.

Telomere length is regulated by TRF1, which binds telomeric DNA, and TIN2, which binds TRF1. Laboratory mice (Mus musculus) have long telomeres, although a related mouse species, Mus spretus, has human-sized telomeres. Because differences in TIN2 might explain these differences in telomere length, we cloned cDNAs encoding murine TIN2s and compared their sequence to that of human TIN2. M. musculus (Mm) and M. spretus TIN2s were >95% identical, but shared only 67% identity with human TIN2. An N-terminal truncation, or N-terminal fragment, of MmTIN2 elongated M. spretus telomeres. These findings suggest that mouse TIN2, like human TIN2, negatively regulates telomere length, and that N-terminal perturbations have dominant-negative effects. Our findings suggest that differences in TIN2 cannot explain the telomere length differences among Homo sapiens, M. musculus, and M. spretus. Nonetheless, M. spretus cells appear be a good system for studying the function of mouse telomere-associated proteins.