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. 2006 Jun;28(2):201-8.
doi: 10.1007/s11357-006-9006-8. Epub 2006 Jun 3.

The age of heterozygosity

Audrey Carrière  1 , Xingxing Liu, Siegfried Hekimi
Affiliations

The age of heterozygosity

Audrey Carrière et al. Age (Dordr). 2006 Jun.

Abstract

Two mutant mouse models of longevity in which the loss of only one copy of the gene leads to a significantly increased lifespan have recently been described: Igf1r (+/-) and mclk1 (+/-). Igf1r encodes a transmembrane receptor kinase for the insulin-like growth factor-1, and mclk1 encodes a hydroxylase that is necessary for the biosynthesis of ubiquinone. Interestingly, the motivation for testing the longevity of both of these mutants came from observations in the nematode Caenorhabditis elegans. IGF-1R protein is homologous to DAF-2 and mCLK1 is the mouse orthologue of the C. elegans enzyme CLK-1. In worms, the homozygous inactivation of both of these longevity genes is viable and no dominant mutations are known. In addition to aging slowly, old mclk1 (+/-) mice were found to undergo loss-of-heterozygosity at the mclk1 locus, which results in clones of mclk1 (-/-) cells in the liver, presumably because mclk1 (-/-) cells can outcompete mclk1 (+/-) cells under certain conditions. We will discuss how these observations suggest novel directions of research, but also call for some caution in the interpretation of past and future results.

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