Using mouse models to investigate the biological and physiological consequences of defects in the Fanconi anaemia/breast cancer DNA repair signalling pathway.

摘要

Fanconi anaemia (FA) is a rare, predominantly autosomal recessive syndrome (with one X-linked form) that results in congenital defects, abnormal haematopoiesis and a greatly increased risk of solid tumours in humans. Mutations in at least 14 different genes have been shown to cause FA, and several of these genes, including FANCJ/BRIP1, FANCD1/BRCA2 and FANCN/PALB2, also predispose to breast cancer in heterozygote carriers. The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA, and thus the FA repair network is intimately linked with hereditary breast cancer. Much remains to be learnt about the functions and interactions of the FA proteins and one experimental approach involves the generation of mice that are deficient in various FA genes. Mouse models for FANCN/PALB2 have recently been generated, including one reported in a recent issue of The Journal of Pathology. Given the pivotal role of the PALB2 protein, which interacts with both BRCA1 and BRCA2, these mice provide valuable insights into the FA phenotype and mechanisms of tumourigenesis caused by disruption of the FA protein network. Copyright (c) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.