Unknown

Dataset Information

0

Phenotype-based identification of mouse chromosome instability mutants.


ABSTRACT: There is increasing evidence that defects in DNA double-strand-break (DSB) repair can cause chromosome instability, which may result in cancer. To identify novel DSB repair genes in mice, we performed a phenotype-driven mutagenesis screen for chromosome instability mutants using a flow cytometric peripheral blood micronucleus assay. Micronucleus levels were used as a quantitative indicator of chromosome damage in vivo. Among offspring derived from males mutagenized with the germline mutagen N-ethyl-N-nitrosourea (ENU), we identified a recessive mutation conferring elevated levels of spontaneous and radiation- or mitomycin C-induced micronuclei. This mutation, named chaos1 (chromosome aberration occurring spontaneously 1), was genetically mapped to a 1.3-Mb interval on chromosome 16 containing Polq, encoding DNA polymerase theta. We identified a nonconservative mutation in the ENU-derived allele, making it a strong candidate for chaos1. POLQ is homologous to Drosophila MUS308, which is essential for normal DNA interstrand crosslink repair and is unique in that it contains both a helicase and a DNA polymerase domain. While cancer susceptibility of chaos1 mutant mice is still under investigation, these data provide a practical paradigm for using a forward genetic approach to discover new potential cancer susceptibility genes using the surrogate biomarker of chromosome instability as a screen.

SUBMITTER: Shima N 

PROVIDER: S-EPMC1462482 | biostudies-other | 2003 Mar

REPOSITORIES: biostudies-other

altmetric image

Publications

Phenotype-based identification of mouse chromosome instability mutants.

Shima Naoko N   Hartford Suzanne A SA   Duffy Ted T   Wilson Lawriston A LA   Schimenti Kerry J KJ   Schimenti John C JC  

Genetics 20030301 3


There is increasing evidence that defects in DNA double-strand-break (DSB) repair can cause chromosome instability, which may result in cancer. To identify novel DSB repair genes in mice, we performed a phenotype-driven mutagenesis screen for chromosome instability mutants using a flow cytometric peripheral blood micronucleus assay. Micronucleus levels were used as a quantitative indicator of chromosome damage in vivo. Among offspring derived from males mutagenized with the germline mutagen N-et  ...[more]

Similar Datasets

| S-EPMC4060510 | biostudies-literature
| S-EPMC2944053 | biostudies-literature
| S-EPMC6689064 | biostudies-literature
| S-EPMC9264972 | biostudies-literature
| S-EPMC6036478 | biostudies-literature
2012-07-03 | E-GEOD-30540 | biostudies-arrayexpress
| S-EPMC7697627 | biostudies-literature
2012-07-04 | GSE30540 | GEO
| S-EPMC6348250 | biostudies-literature
| S-EPMC8494802 | biostudies-literature