A Conditional Mouse Model for Measuring the Frequency of Homologous Recombination Events In Vivo in the Absence of Essential Genes

Abstract

The ability to detect and repair DNA damage is crucial to the prevention of various diseases. Loss of function of genes involved in these processes is known to result in significant developmental defects and/or predisposition to cancer. One such DNA repair mechanism, homologous recombination, has the capacity to repair a wide variety of lesions. Knockout mouse models of genes thought to be involved in DNA repair processes are frequently lethal, making in vivo studies very difficult, if not impossible. Therefore, we set out to develop an in vivo conditional mouse model system to facilitate investigations into the involvement of essential genes in homologous recombination. To test our model, we measured the frequency of spontaneous homologous recombination using the pink-eyed unstable mouse model, in which we conditionally excised either Blm or full-length Brca1 (breast cancer 1, early onset). These two genes are hypothesized to have opposing roles in homologous recombination. In summary, our in vivo data supports in vitro studies suggesting that BLM suppresses homologous recombination, while full-length BRCA1 promotes this process.

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00848-10.

ACKNOWLEDGMENTS

This work was supported by the National Institute of Environmental Health Sciences (grant K22ES012264 to A.J.R.B.), an American Cancer Society Institutional Research Grant (ACS-IRG-00-173-04) pilot project award (to A.J.R.B.), and the National Institute of Aging (grant T32AG021890 to A.D.B.).

We thank Jo Ann Martinez for helping to establish the mouse lines.