APRT: a versatile in vivo resident reporter of local mutation and loss of heterozygosity

Environmental and Molecular Mutagenesis
P J StambrookJ A Tischfield

Abstract

We describe an in vivo mutagenesis model that utilizes reverse mutation and forward mutation at the endogenous Aprt locus. Reverse mutation provides an in situ method for detecting environments or agents that cause point mutations. Forward mutation detects large chromosomal events, including mitotic recombination, chromosome loss, and large multilocus deletion, all of which can lead to loss of heterozygosity. Detection of reverse mutation in vivo is based on the differential capacity of Aprt and Aprt cells to sequester radiolabeled adenine by catalyzing its conversion to adenosine monophosphate with subsequent incorporation into nucleic acids. Cells lacking APRT activity cannot accumulate exogenously administered, tagged adenine, whereas Aprt+ cells can and will thereby become marked. Thus, genetically modified mice with mutant but revertible Aprt alleles should be a useful vehicle for in situ detection of mutagenic activity in the whole animal. the feasibility of this model has been illustrated, first, by showing that APRT-deficient mice are viable and, second, by demonstrating that the minority of Aprt+ cells within a chimeric tumor growing in an Aprt+ mouse can be selectively labeled following IP injection of [14C]-adenine a...Continue Reading

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Citations

Feb 3, 2005·Environmental and Molecular Mutagenesis·Masamitsu Honma
May 9, 2002·Mutation Research·Li LiangJay A Tischfield
Sep 5, 2001·Kidney International·A P EvanJ A Tischfield
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Aug 18, 2006·Mutation Research·Y HongP J Stambrook
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Oct 14, 2004·Oncogene·Changshun ShaoJay A Tischfield
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Jun 13, 2021·Environmental and Molecular Mutagenesis·Javier R RevolloVasily N Dobrovolsky
Aug 6, 2005·Mutation Research·Iain B LambertGeorge R Douglas

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