Paradoxical decrease in mutant frequencies and chromosomal rearrangements in a transgenic lacZ reporter gene in Ku80 null mice deficient in DNA double strand break repair

Lynne D Rockwood; André Nussenzweig; Siegfried Janz

doi:10.1016/S0027-5107(03)00108-8

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Journal article

Paradoxical decrease in mutant frequencies and chromosomal rearrangements in a transgenic lacZ reporter gene in Ku80 null mice deficient in DNA double strand break repair

Lynne D Rockwood, André Nussenzweig and Siegfried Janz

Mutation research, Vol.529(1), pp.51-58

2003

DOI: 10.1016/S0027-5107(03)00108-8

PMID: 12943919

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Abstract

Repair of DNA double strand breaks (DSB), either by homologous recombination (HR) or nonhomologous end-joining (NHEJ), is essential to maintain genomic stability. To examine the impact of NHEJ deficiency on genomic integrity in Ku80 null (Ku −) mice, the chromosomally integrated shuttle vector pUR288, which includes a lacZ reporter gene, was used to measure mutations in vivo. Unexpectedly, a significant decrease was found in mutant frequencies of Ku − liver (5.04×10 −5) and brain (4.55×10 −5) compared to tissues obtained from normal (Ku +) littermates (7.92×10 −5and 7.30×10 −5, respectively). No significant difference was found in mutant frequencies in spleen from Ku − (7.21×10 −5) and Ku + mice (8.16×10 −5). The determination of the mutant spectrum in lacZ revealed the almost complete absence of chromosomal rearrangements (R) in Ku − tissues (0.5%, 3/616), a notable distinction from Ku + controls (16.7%, 104/621). These findings suggest that accurate repair of DSB by HR and elimination of cells with unrepaired DNA damage by apoptosis are capable of maintaining genomic stability of the lacZ reporter in Ku − mice.

In vivo mutant frequency

Transgenic shuttle vector-based mutagenesis assay

Ku80 deficiency

Genomic instability

Details

Title: Subtitle: Paradoxical decrease in mutant frequencies and chromosomal rearrangements in a transgenic lacZ reporter gene in Ku80 null mice deficient in DNA double strand break repair
Creators: Lynne D Rockwood - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NCI, Room 2B10, Building 37, Bethesda, MD 20892-4256, USA
André Nussenzweig - Experimental Immunology Branch, Bethesda, MD 20892, USA
Siegfried Janz - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NCI, Room 2B10, Building 37, Bethesda, MD 20892-4256, USA
Resource Type: Journal article
Publication Details: Mutation research, Vol.529(1), pp.51-58
Publisher: Elsevier B.V
DOI: 10.1016/S0027-5107(03)00108-8
PMID: 12943919
ISSN: 0027-5107
eISSN: 1873-135X
Language: English
Date published: 2003
Academic Unit: Pathology
Record Identifier: 9984083208202771

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