TELOMERE LENGTH REGULATION IN MICE IS LINKED TO A NOVEL CHROMOSOME LOCUS

Little is known about the mechanisms that regulate species-specific te lomere length, particularly in mammalian species. The genetic regulati on of telomere length was therefore investigated by using two inter-fe rtile species of mice, which differ in their telomere length. Mus musc ulus (telomere length >25 kb) and Mus spretus (telomere length 5-15 kb ) were used to generate F1 crosses and reciprocal backcrosses, which w ere then analyzed for regulation of telomere length. This analysis ind icated that a dominant and trans-acting mechanism exists capable of ex tensive elongation of telomeres in somatic cells after fusion of paren tal germline cells with discrepant telomere lengths. A genome wide scr een of interspecific crosses, using M. spretus as the recurrent parent , identified a 5-centimorgan region on distal chromosome 2 that predom inantly controls the observed species-specific telomere length regulat ion. This locus is distinct from candidate genes encoding known telome re-binding proteins or telomerase components. These results demonstrat e that an unidentified gene(s) mapped to distal chromosome 2 regulates telomere length in the mouse.