Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11ATLD1/ATLD1 mice Journal Article
| Authors: | Theunissen, J. W. F.; Kaplan, M. I.; Hunt, P. A.; Williams, B. R.; Ferguson, D. O.; Alt, F. W.; Petrini, J. H. J. |
| Article Title: | Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11ATLD1/ATLD1 mice |
| Abstract: | In this study, mice expressing one of the two Mre11 alleles inherited in the human ataxia-telangiectasia like disorder (A-TLD) were derived. The mutation had a profound maternal effect on embryonic viability, revealing an acute requirement for Mre11 complex function in early embryogenesis. Mre11 ATLD1/ATLD1 mice exhibited several indices of impaired ATM function. The mice also exhibited pronounced chromosomal instability. Despite this phenotypic spectrum, the animals were not prone to malignancy. These data indicate that defective cell cycle checkpoints and chromosomal instability are insufficient to significantly enhance the initiation of tumorigenesis. In contrast, the latency of malignancy in p53+/- mice was dramatically reduced. We propose that in Mre11ATLD1/ATLD1 mice, genome instability and cell cycle checkpoint defects reduce viability in early embryos and in proliferating cells, while promoting malignancy in the context of an initiating lesion. |
| Keywords: | controlled study; survival rate; gene mutation; human cell; dna-binding proteins; nonhuman; cell proliferation; animal cell; phenotype; animals; mice; mre11 protein; allele; cell viability; dna damage; cells, cultured; cell cycle; cancer susceptibility; gene expression; embryo; animal model; embryo development; gene function; protein p53; carcinogenesis; animalia; lymphoma; fibroblasts; atm protein; dna repair enzymes; tumor suppressor protein p53; chromosomal instability; pregnancy; fertility; karyotyping; genes, cdc; ataxia telangiectasia; chromosomes, mammalian; chromosome damage; lymphomagenesis; humans; human; female; article |
| Journal Title: | Molecular Cell |
| Volume: | 12 |
| Issue: | 6 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2003-12-01 |
| Start Page: | 1511 |
| End Page: | 1523 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(03)00455-6 |
| PUBMED: | 14690604 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
