Evidence that the keratinocyte colony number is genetically controlled

We tested five inbred strains and two outbred stocks of female mice in a quantitative assay for clonogenic keratinocytes from the cutaneous epithelium. We found three significantly different subsets of colony counts such that: C57BL/6 C3H = DBA/2 = SENCAR = BALB/c < FVB = CD^-1 in culture conditions optimized for CD^-10. C57BL/6 and BALB/c, two inbred parental strains, were chosen for further analysis. The Fl generation of these two parental strains had an intermediate number of colonies. The keratinocyte colony number from the two backcross generations was significantly different, while the colony number in the F2 generation was intermediate between the two backcrosses. We conclude that the number of keratinocyte colonies represents a new genetically definable quantitative trait. Analysis suggests that this trait is multigenic where the genes have an additive but not necessarily equal effect. We have therefore laid the foundation for identifying these stem cell regulatory genes, which may provide a new perspective on the mechanism of carcinogenesis and a new target for gene therapy.