PALB2 interacts with BRCA1 and BRCA2 in supercomplexes involved in DNA repair 
via homologous recombination. Heterozygous germline mutations in PALB2 confer a 
moderate risk of breast cancer, while biallelic PALB2 mutations are linked to a 
severe form of Fanconi anaemia characterized by early childhood solid tumours 
and severe chromosomal instability. In contrast to BRCA1- or BRCA2-associated 
cancers, breast tumours in heterozygous PALB2 mutation carriers do not show loss 
of the wild-type allele, suggesting PALB2 might be haploinsufficient for tumour 
suppression. To study the role of PALB2 in development and tumourigenesis, we 
have generated Palb2(GT) mouse mutants using a gene trap approach. Whereas 
Palb2(GT/GT) homozygous mutant embryos died at mid-gestation due to massive 
apoptosis, Palb2(GT/+) heterozygous mice were viable and did not show any 
obvious abnormalities. Deletion of p53 alleviated the phenotype of Palb2(GT/GT) 
embryos, but did not rescue embryonic lethality. In addition, loss of p53 did 
not significantly collaborate with Palb2 heterozygosity in tumourigenesis in 
heterozygous or homozygous p53 knockout mice. Tumours arising in Palb2(GT/+) 
;p53(+/-) or Palb2(GT/+) ;p53(-/-) compound mutant mice retained the wild-type 
Palb2 allele and did not display increased genomic instability.