Early aging-associated phenotypes in Bub3/Rae1 haploinsufficient mice

Darren J Baker, Karthik B. Jeganathan, Liviu Malureanu, Carmen M Terzic, Andre Terzic, Jan Van Deursen

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134 Citations (Scopus)

Abstract

Aging is a highly complex biological process that is believed to involve multiple mechanisms. Mice that have small amounts of the mitotic checkpoint protein BubR1 age much faster than normal mice, but whether other mitotic checkpoint genes function to prevent the early onset of aging is unknown. In this study, we show that several aging-associated phenotypes appear early in mice that are double haploinsufficient for the mitotic checkpoint genes Bub3 and Rae1 but not in mice that are single haploinsufficient for these genes. Mouse embryonic fibroblasts (MEFs) from Bub3/Rae1 haploinsufficient mice undergo premature senescence and accumulate high levels of p19, p53, p21, and p16, whereas MEFs from single haploinsufficient mice do not. Furthermore, although BubR1 hypomorphic mice have less aneuploidy than Bub3/Rae1 haploinsufficient mice, they age much faster. Our findings suggest that early onset of aging-associated phenotypes in mice with mitotic checkpoint gene defects is linked to cellular senescence and activation of the p53 and p16 pathways rather than to aneuploidy.

Original languageEnglish (US)
Pages (from-to)529-540
Number of pages12
JournalJournal of Cell Biology
Volume172
Issue number4
DOIs
StatePublished - Feb 13 2006

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Phenotype
M Phase Cell Cycle Checkpoints
Aneuploidy
Genes
Fibroblasts
Biological Phenomena
Cell Aging
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Early aging-associated phenotypes in Bub3/Rae1 haploinsufficient mice. / Baker, Darren J; Jeganathan, Karthik B.; Malureanu, Liviu; Terzic, Carmen M; Terzic, Andre; Van Deursen, Jan.

In: Journal of Cell Biology, Vol. 172, No. 4, 13.02.2006, p. 529-540.

Research output: Contribution to journalArticle

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