High frequency "switching" at the adenine phosphoribosyltransferase locus in multipotent mouse teratocarcinoma stem cells.

Clones of multipotent mouse tetratocarcinoma stem cells, presumptively heterozygous at the adenine phosphoribosyltransferase (APRT) locus (EC 2.4.2.7), were selected for partial resistance to the purine analog 2',6'-diaminopurine (DAP). All had approximately 50% APRT activity as compared to the parental line and were found to segregate homozygous deficient cells at a high frequency (approximately 10(-2]. Homozygous deficient cells were isolated from one of the heterozygotes and were found to fall into a single class characterized by residual activity and the segregation of revertants at an equally high frequency. The revertants in turn gave rise to full mutants at comparably high frequencies. Chromosomal changes detectable with the light microscope were not associated with these transitions. Physical characterization of the APRT enzymes derived from mutant, revertant, and wild-type cells did not reveal any differences. We conclude that the reversible "switching" between heterozygosity and homozygosity is attributable to some form of gene inactivation and reactivation rather than to classical mutational events.