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gadzooks!

Nature Genetics volume 23, pages 10–11 (1999)Cite this article

The ubiquitin-proteasome pathway of protein degradation is essential for eukaryotes and involves cellular machinery as elaborate as that required by protein synthesis. Critical molecular steps, however, are emerging from the discovery of mutations that cause problems ranging from cancer to hypertension to fat facets1. On page 47 of this issue, Kazumasa Saigoh and colleagues2 broaden the spectrum by discovering that a mutation in the ubiquitin carboxy-terminal hydrolase gene (Uchl1) causes gracile axonal dystrophy (gad) in mice.

The identity of the gad gene defect, therefore, comes as a welcome surprise. Saigoh et al. homed in on the gad locus on chromosome 5 by following co-inheritance of the gad phenotype with polymorphic DNA markers in a classic genetic linkage-based cloning strategy. Their reward is an in-frame deletion in Uchl1 that results in a truncated form of ubiquitin hydrolase, a thiol protease that participates in ubiquitin biosythesis and in protein degradation.

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  1. Molecular Neurogenetics Unit, Massachusetts General Hospital, 13th Street, Charlestown, 02129, Massachusetts, USA

    Marcy E MacDonald

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  1. Marcy E MacDonald
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MacDonald, M. gadzooks!. Nat Genet 23, 10–11 (1999). https://doi.org/10.1038/12602

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