Loss of heterozygosity and point mutation at Aprt locus in T cells and fibroblasts of Pms2-/- mice

Changshun Shao, Moying Yin, Li Deng, Peter J. Stambrook, Thomas C Doetschman, Jay A. Tischfield

Research output: Contribution to journalArticle

Abstract

Mice null for the Pms2 mismatch repair (MMR) gene exhibit a predisposition to lymphoma, microsatellite repeat instability, and failure of spermatogenesis. To study the role of Pms2 in the maintenance of in vivo genomic integrity in somatic cells, we characterized Aprt mutations in T cells and fibroblasts of 129 × C3H Pms2-/- Aprt-/- mice. The spontaneous frequency of DAP-resistant T lymphocytes, as a consequence of APRT-deficiency, was increased threefold. Point mutation, which accounted for less than 20% of the DAPr mutant clones in Pms2+/+ mice, was predominant in the mutant T cell clones from Pms2-/- mice. These point mutations were predominantly TA to CG transitions. Fibroblasts of Pms2-/- mice exhibited only a modest increase in the frequency of clones with point mutations, such that mitotic recombination was still the primary cause of APRT deficiency. Thus, the mutator phenotype as a consequence of PMS2 deficiency is tissue-dependent, which may be related to the tissue-specific tumor proneness of Pros2-/- mice.

Original languageEnglish (US)
Pages (from-to)2840-2845
Number of pages6
JournalOncogene
Volume21
Issue number18
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Loss of Heterozygosity
Point Mutation
Fibroblasts
T-Lymphocytes
Clone Cells
Microsatellite Instability
DNA Mismatch Repair
Spermatogenesis
Microsatellite Repeats
Genetic Recombination
Lymphoma
Maintenance
Phenotype
Mutation
Genes
Neoplasms

Keywords

  • APRT
  • Loss of heterozygosity
  • Mismatch repair
  • Mouse model
  • PMS2
  • Somatic mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Loss of heterozygosity and point mutation at Aprt locus in T cells and fibroblasts of Pms2-/- mice. / Shao, Changshun; Yin, Moying; Deng, Li; Stambrook, Peter J.; Doetschman, Thomas C; Tischfield, Jay A.

In: Oncogene, Vol. 21, No. 18, 01.01.2002, p. 2840-2845.

Research output: Contribution to journalArticle

Shao, Changshun ; Yin, Moying ; Deng, Li ; Stambrook, Peter J. ; Doetschman, Thomas C ; Tischfield, Jay A. / Loss of heterozygosity and point mutation at Aprt locus in T cells and fibroblasts of Pms2-/- mice. In: Oncogene. 2002 ; Vol. 21, No. 18. pp. 2840-2845.
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