Loss of p53 partially rescues embryonic development of Palb2 knockout mice but does not foster haploinsufficiency of Palb2 in tumour suppression

J Pathol. 2011 May;224(1):10-21. doi: 10.1002/path.2861. Epub 2011 Mar 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Embryo Loss / genetics
  • Embryonic Development / genetics
  • Embryonic Development / physiology*
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Gene Deletion
  • Genes, p53
  • Genomic Instability / genetics
  • Haploinsufficiency / genetics*
  • Heterozygote
  • Lymphoma / genetics
  • Mammary Neoplasms, Experimental / genetics
  • Mice
  • Mice, Knockout
  • Thymus Neoplasms / genetics
  • Tumor Suppressor Protein p53 / deficiency*
  • Tumor Suppressor Proteins / deficiency*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology


  • Fanconi Anemia Complementation Group N Protein
  • Palb2 protein, mouse
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins