| First Author | Liang L | Year | 2000 |
| Journal | Environ Mol Mutagen | Volume | 35 |
| Issue | 2 | Pages | 150-7 |
| PubMed ID | 10712749 | Mgi Jnum | J:61284 |
| Mgi Id | MGI:1354644 | Citation | Liang L, et al. (2000) In vivo loss of heterozygosity in T-cells of B6C3F1 Aprt(+/-) mice. Environ Mol Mutagen 35(2):150-7 |
| abstractText | We have used B6C3F1 mice heterozygous at Aprt (adenine phosphoribosyltransferase) as a model to study in vivo loss of heterozygosity (LOH) in normal splenic T-lymphocytes. APRT-deficient T-cells were selected in medium containing 50 &mgr;g/ml 2, 6-diaminopurine (DAP), an adenine analog that is toxic only to cells with APRT enzyme activity. DAP-resistant (DAP(r)) T-cell variants were recovered at an average frequency of 3 x 10(-5) from 21 B6C3F1 Aprt(+/-) mice. Allele-specific PCR of Aprt showed that about 70% of 122 DAP(r) colonies were caused by loss of the nontargeted Aprt allele (Aprt(+)). Analysis of microsatellite markers along the length of chromosome 8 suggested that mitotic recombination, or chromosome loss, with or without duplication of the remaining chromosome are the predominant mechanisms resulting in loss of Aprt(+). DNA sequencing of Aprt RT-PCR products from the DAP(r) variants that retained Aprt(+) indicated that point mutation as well as other mechanisms could cause this second class of variants. The high spontaneous frequency of in vivo Aprt LOH in mouse T-cells, mediated by LOH mechanisms that are also known to produce human cancers, suggests that the Aprt heterozygous mouse is a valid model for studying the diversity of mechanisms for in vivo somatic mutagenesis. Copyright 2000 Wiley-Liss, Inc. |
