Biallelic methylation and silencing of mouse Aprt in normal kidney cells

Heritable gene silencing is an important mechanism of tumor suppressor gene inactivation in a variety of human dancers. In the present study, we show that methylation-associated silencing of the autosomal adenine phosphoribos yltransferase (Aprt) locus occurs in primary mouse kidney cells. Aprt-defic ient cells were isolated from mice that were heterozygous for Aprt, ie., th ey contained one wild-type Aprt allele and one targeted allele bearing an i nsertion of the bacterial neo gene. Although silencing of the wild-type all ele alone was sufficient for the cells to become completely Aprt-deficient, biallelic methylation of the promoter region was found to occur, Moreover, despite the absence of selective pressure against the targeted allele, phe notypic silencing of the inserted neo gene accompanied silencing of the wil d-type Aprt allele, A potential role for allelic homology in these events i s discussed.