THE CRYPT CYCLE AND THE ASYMPTOTIC DYNAMICS OF THE PROPORTION OF DIFFERENTLY SIZED MUTANT CRYPT CLONES IN THE MOUSE INTESTINE

The dynamics of clones of intestinal epithelial crypts populated by mu tant stem cells offers the hope of new and independent evidence of con tinued crypt replication throughout adult life, an important predictio n of recent models of intestinal stem cell biology. It is shown here t hat the experimentally most tractable measurement - scoring of the fra ction of groups of mutant crypts found as isolated singletons, pairs, or clusters of greater than or equal to 3 mutant crypts - should tend to an asymptotic distribution as animals age. In particular, if the ra te of mutation is low relative to the rate of crypt production then a, 1/2, 1/6 and 1/3 of groups of mutant crypts should be found as single tons, pairs, and larger clusters, respectively, as animals reach old a ge. Such a result is not immediately obvious, and if obtained from an experiment could easily be misinterpreted as implying that the crypt c ycle must slow radically as animals age.