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.

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