Short Report

Oncogene (2005) 24, 3842−3846. doi: 10.1038/sj.onc.1208533 Published online 28 February 2005
Published online 28 February 2005

Brca2 deficiency in the murine small intestine sensitizes to p53-dependent apoptosis and leads to the spontaneous deletion of stem cells

Trevor Hay1, Teresa Patrick1, Douglas Winton2, Owen J Sansom1 and Alan R Clarke1

  1. 1School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK
  2. 2Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, UK

Correspondence: AR Clarke, E-mail: [email protected]

Received 24 November 2004; Revised 11 January 2005; Accepted 14 January 2005; Published online 28 February 2005.



The gene encoding the human BRCA2 tumour suppressor is mutated in a number of different tumour types, most notably inherited breast cancers. The primary role of BRCA2 is thought to lie in the maintenance of genomic stability via its role in the homologous recombination pathway. We generated mice in which Brca2 was deleted from virtually all cells within the adult small intestine, using a CYP1A1-driven Cre-Lox approach. We noted a significant p53-dependent increase in the levels of spontaneous apoptosis which persisted for several months after removal of the gene and ultimately we observed the spontaneous deletion of Brca2-deficient stem cells. Brca2 deficiency did not lead to gross changes in intestinal physiology but did enhance sensitivity to a variety of DNA crosslinking agents. Taken together, our results indicate that Brca2 plays an important role in the response to DNA damage in the small intestine. Furthermore, we show that Brca2 deficiency results in the spontaneous deletion of stem cells, thereby protecting the small intestine against tumorigenesis.


Brca2, p53, small intestine, apoptosis, DNA damage

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