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. 2004 Jul;36(7):744-9.
doi: 10.1038/ng1382. Epub 2004 Jun 20.

BubR1 Insufficiency Causes Early Onset of Aging-Associated Phenotypes and Infertility in Mice

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BubR1 Insufficiency Causes Early Onset of Aging-Associated Phenotypes and Infertility in Mice

Darren J Baker et al. Nat Genet. .

Abstract

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.

Comment in

  • Aging counts on chromosomes.
    Fernandez-Capetillo O, Nussenzweig A. Fernandez-Capetillo O, et al. Nat Genet. 2004 Jul;36(7):672-4. doi: 10.1038/ng0704-672. Nat Genet. 2004. PMID: 15226747 No abstract available.
  • The many sides of CIN.
    Knouse KA, Amon A. Knouse KA, et al. Nat Rev Mol Cell Biol. 2013 Oct;14(10):611. doi: 10.1038/nrm3666. Nat Rev Mol Cell Biol. 2013. PMID: 24061225 Free PMC article. No abstract available.

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