X-Message-Number: 12421 Date: Tue, 14 Sep 1999 18:29:10 -0400 From: Jan Coetzee <> Subject: Prematurely aged rodents Deletion of Ku86 causes early onset of senescence in mice Hannes Vogel*, Dae-Sik Lim,, Gerard Karsenty , Milton Finegold*, and Paul Hasty, * Department of Pathology and Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX 77030; and Lexicon Genetics, 4000 Research Forest Drive, The Woodlands, TX 77381-4287 Edited by Philip Leder, Harvard Medical School, Boston, MA, and approved July 7, 1999 (received for review May 24, 1999) DNA double-strand breaks formed during the assembly of antigen receptors or after exposure to ionizing radiation are repaired by proteins important for nonhomologous end joining that include Ku86, Ku70, DNA-PKCS, Xrcc4, and DNA ligase IV. Here we show that ku86-mutant mice, compared with control littermates, prematurely exhibited age-specific changes characteristic of senescence that include osteopenia, atrophic skin, hepatocellular degeneration, hepatocellular inclusions, hepatic hyperplastic foci, and age-specific mortality. Cancer and likely sepsis (indicated by reactive immune responses) partly contributed to age-specific mortality for both cohorts, and both conditions occurred earlier in ku86/ mice. These data indicate that Ku86-dependent chromosomal metabolism is important for determining the onset of age-specific changes characteristic of senescence in mice. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=12421