Telomere length regulation in mice is linked to a novel chromosome locus

Telomere length regulation in mice is linked to a novel chromosome locus

^†Rowe Program in Genetics, Departments of Biological Chemistry and Medicine University of California, Davis, Davis, CA 95616; ^‡Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; ^¶Terry Fox Laboratory for Hematology/Oncology, British Columbia Cancer Research Center, 601 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; and ^‖National Institute on Aging, National Institutes of Health, Bethesda, MD 20892

Edited by Irving L. Weissman, Stanford University School of Medicine, Stanford, CA, and approved, May 20, 1998 (received for review September 15, 1997)

Abstract

Little is known about the mechanisms that regulate species-specific telomere length, particularly in mammalian species. The genetic regulation of telomere length was therefore investigated by using two inter-fertile species of mice, which differ in their telomere length. Mus musculus (telomere length >25 kb) and Mus spretus (telomere length 5–15 kb) were used to generate F1 crosses and reciprocal backcrosses, which were then analyzed for regulation of telomere length. This analysis indicated that a dominant and trans-acting mechanism exists capable of extensive elongation of telomeres in somatic cells after fusion of parental germline cells with discrepant telomere lengths. A genome wide screen of interspecific crosses, using M. spretus as the recurrent parent, identified a 5-centimorgan region on distal chromosome 2 that predominantly controls the observed species-specific telomere length regulation. This locus is distinct from candidate genes encoding known telomere-binding proteins or telomerase components. These results demonstrate that an unidentified gene(s) mapped to distal chromosome 2 regulates telomere length in the mouse.

Footnotes

↵ * These authors contributed equally to this work.
↵ § To whom reprint requests should be addressed. e-mail Karen_Hathcock{at}nih.gov.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: cM, centimorgan; TRF, telomere restriction fragment; EST, expressed sequence tag.