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The age of heterozygosity

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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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Abbreviations

IGF-1:

insulin-like growth factor-1

LOH:

loss-of-heterozygosity

ES:

embryonic stem

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Authors and Affiliations

  1. Department of Biology, McGill University, 1205 avenue Docteur Penfield, H3A 1B1, Montreal, Quebec, Canada

    Audrey Carrière, Xingxing Liu & Siegfried Hekimi

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  1. Audrey Carrière
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  2. Xingxing Liu
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  3. Siegfried Hekimi
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Correspondence to Siegfried Hekimi.

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Carrière, A., Liu, X. & Hekimi, S. The age of heterozygosity. AGE 28, 201–208 (2006). https://doi.org/10.1007/s11357-006-9006-8

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  • DOI: https://doi.org/10.1007/s11357-006-9006-8

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