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 Posted: Tue Oct 07, 2008 6:56 pm Post subject: BubR1 insufficiency causes early onset of aging-associated p |
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Nat Genet. 2004 Jul;36(7):744-9. Epub 2004 Jun 20. Links
Comment in:
Nat Genet. 2004 Jul;36(7):672-4.
BubR1 insufficiency causes early onset of aging-associated phenotypes
and infertility in mice.Baker DJ, Jeganathan KB, Cameron JD, Thompson
M, Juneja S, Kopecka A, Kumar R, Jenkins RB, de Groen PC, Roche P, van
Deursen JM.
[1] Departments of Pediatric and Adolescent Medicine, Mayo Clinic, 200
First Street SW, Rochester, Minnesota 55905, USA. [2] Departments of
Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW,
Rochester, Minnesota 55905, USA.
Faithful segregation of replicated chromosomes is essential for
maintenance of genetic stability and seems to be monitored by several
mitotic checkpoints. Various components of these checkpoints have been
identified in mammals, but their physiological relevance is largely
unknown. Here we show that mutant mice with low levels of the spindle
assembly checkpoint protein BubR1 develop progressive aneuploidy along
with a variety of progeroid features, including short lifespan,
cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat
and impaired wound healing. Graded reduction of BubR1 expression in
mouse embryonic fibroblasts causes increased aneuploidy and
senescence. Male and female mutant mice have defects in meiotic
chromosome segregation and are infertile. Natural aging of wild-type
mice is marked by decreased expression of BubR1 in multiple tissues,
including testis and ovary. These results suggest a role for BubR1 in
regulating aging and infertility.
PMID: 15208629 [PubMed - indexed for MEDLINE] |
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