Progression, following Cre reversion, of a β-gal+ stem cell to a field of β-gal+ crypts. (A) Diagram summarizing the Pms2
cre mouse system combined with a conditional Apc allele. An out-of-frame cre gene is located at the Pms2 locus. Upon frameshift mutation within the mononucleotide repeat (A12), Cre protein becomes active and recombines the conditional target allele Apc and the reporter allele LacZ. (B) Cre reversion occurs stochastically at low frequency, resulting in a single Apc-deficient β-gal+ cell within a crypt. Only Cre activation in a stem cell will have the chance to spread throughout the crypt. (C) The end product of crypt succession by a single β-gal+ stem cell, namely, a monoclonal, β-gal+ crypt. (D) The end product of crypt fission of the monoclonal, β-gal+ crypt producing a pair of neighboring, Apc-deficient β-gal+ crypts. (E) The consequence of continued crypt fission resulting in a field of Apc-deficient β-gal+ crypts.