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.