Clonal analysis of intestinal crypt populations in mouse aggregation chimaeras

Abstract

The epithelium of each individual intestinal crypt in adult mouse aggregation chimaeras is composed of cells of a single parental genotype (Ponder et al. 1985). Using a carbohydrate polymorphism recognized by Dolichos biflorus agglutinin as a strain-specific marker on entire sheets of intestinal mucosa, we have analysed the two-dimensional mosaic patterns of patches of the chimaeric intestinal crypt population. The relative proportions of each genotype varied greatly along the length of any one intestine. In chimaeras with highly unbalanced proportions, the minority component occurred as discrete patches. Patches of single or a few crypts were most frequent, but a smaller number of much larger patches was always present. The size frequency distribution of discrete patches was highly concave and departed significantly from a geometric distribution (a model for non-differential proliferation), but fitted the more skewed negative binomial model. The data are consistent with the interpretation that most progenitor crypts never or rarely divide, while a minority proliferate to a greater extent. We discuss ways in which our system could be analysed further to examine this interpretation. Our results also support Whitten's (1978) conclusion from a computer simulation that the mean patch size, as it has previously been used in statistical analyses of chimaeric tissue, 'is not a reliable statistic on which to judge mosaicism'.