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Genetic Loci That Influence Cause of Death in a Heterogeneous Mouse Stock

¹ Division on Aging, Harvard Medical School, Boston, Massachusetts.
² University of Michigan Institute of Gerontology, Ann Arbor.
³ University of Michigan Geriatrics Center, Ann Arbor.
⁴ Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor.
⁵ Department of Pathology, University of Michigan School of Medicine, and Ann Arbor VA Medical Center.

Address correspondence to Richard A. Miller, Rm. 5316 CCGCB, Box 0940, University of Michigan, 1500 East Medical Center Dr., Ann Arbor, MI 48109-0940. E-mail: millerr{at}umich.edu

A genome scan was conducted to seek evidence for polymorphic genes that influence cause of death in mice produced by a cross between CB6F1 females and C3D2F1 males. Loci on chromosomes 1 and 4 were found to modulate risk of lymphoma. A locus on chromosome 4 influenced risk of mammary adenocarcinoma among multiparous female mice, but had no significant effect in virgin females. A chromosome 4 locus was found to modulate risk of death from either hemangiosarcoma or fibrosarcoma. A suggestive linkage was noted (at p =.09) between a marker on chromosome 11 and hepatocellular carcinoma. Lastly, a locus on chromosome 6 was noted to influence the likelihood that pulmonary adenocarcinoma would be present at death. The collection of normal and neoplastic tissues from 1004 terminal necropsies, together with genetic information, provides a valuable resource for further studies of the genetic influences on late-life diseases in mice.