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 Mre11(ATLD1/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.
We have not found any resources mentioned in this publication.
SciCrunch is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to SciCrunch, however this is not currently a free service.