Gene Thought to Control Aging

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BubR1 insufficiency causes early onset of aging-associated phenotypes

and infertility in mice.

Baker DJ, Jeganathan KB, Cameron JD, M, Juneja S, Kopecka A,

Kumar R, 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.

Nat Genet. 2004 Jul;36(7):744-9. Epub 2004 Jun 20.

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.

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