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Publication : Biallelic methylation and silencing of mouse Aprt in normal kidney cells.

First Author  Rose JA Year  2000
Journal  Cancer Res Volume  60
Issue  13 Pages  3404-8
PubMed ID  10910047 Mgi Jnum  J:63479
Mgi Id  MGI:1861052 Citation  Rose JA, et al. (2000) Biallelic methylation and silencing of mouse Aprt in normal kidney cells. Cancer Res 60(13):3404-8
abstractText  Heritable gene silencing is an important mechanism of tumor suppressor gene inactivation in a variety of human cancers. In the present study, we show that methylation-associated silencing of the autosomal adenine phosphoribosyltransferase (Aprt) locus occurs in primary mouse kidney cells. Aprt-deficient cells were isolated from mice that were heterozygous for Aprt, i.e., they contained one wild-type Aprt allele and one targeted allele bearing an insertion of the bacterial neo gene. Although silencing of the wild-type allele 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, phenotypic silencing of the inserted neo gene accompanied silencing of the wild-type Aprt allele. A potential role for allelic homology in these events is discussed.
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