Abstract
Cellular mosaicism resulting from X-chromosome inactivation in heterozygous females1 can be shown histochemically2–4; using this approach we have demonstrated age-related gene reactivation5 and tumour clonality6. We now show in female mice heterozygous for reduced expression of glucose-6-phosphate dehydrogenase (G6PD) activity that colonic epithelial cells express either normal or low enzyme activity, and form patches composed of multiple crypts of uniform phenotype. We also show that a low-enzyme colonic epithelial cell phenotype can be induced in normal mice by car-cinogen treatment, these cells again occur in patches, but are restricted to scattered single crypts, the frequency of which is related to treatment. A small proportion of colonic tumours in carcinogen treated normal mice are also of low-enzyme phenotype. We conclude that we have visualized the effects of a sporadic carcinogen induced somatic mutation in the G6PD gene of crypt stem cells and that a single stem cell maintains each colonic crypt. This inducible defective activity of a ubiquitous 'housekeeping' enzyme provides a somatic clonal marker system of wide potential application.
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Griffiths, D., Davies, S., Williams, D. et al. Demonstration of somatic mutation and colonic crypt clonality by X-linked enzyme histochemistry. Nature 333, 461–463 (1988). https://doi.org/10.1038/333461a0
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DOI: https://doi.org/10.1038/333461a0
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