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Cancer Research Campaign Human Cancer Genetics Research Group, Cambridge University, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom [L. S. F., B. A. J. P.]; Wellcome/Cancer Research Campaign Institute of Cancer and Developmental Biology and Department of Genetics, Cambridge University, Cambridge CB2 1QR, United Kingdom [F. C. T., M. B. L. C., S. M. H., M. J. E.]; Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom [K. J. P., V. P. C. C. Y., H. L., A. R. V.]; Sequana Therapeutics, La Jolla, California 92037 [K. J. A.]; and Physiological Laboratory, Cambridge University, Cambridge CB2 3EG, United Kingdom [W. H. C.]
Inherited mutations in the BRCA2 gene predispose women to breast and ovarian cancer. We created a mutation in the mouse Brca2 gene that terminates translation in exon 11 at 45% of the normal transcript length. Ninety % of Brca2tm1Cam homozygous mutant mice die prenatally or perinatally. The location of the Brca2tm1Cam mutation differs from those reported previously, and this phenotype suggests a correlation with genotype analogous to that previously reported in humans. Although heterozygote mice have remained free of tumors for 10 months, Brca2tm1Cam homozygous mutants that survived to adulthood died with thymic lymphomas between 12 and 14 weeks of age.
1 This research was supported by a programme grant from the Cancer Research Campaign [CRC] to B. A. J. P., The Wellcome Trust, and the Medical Research Council. L. S. F. is a Hitchings-Elion Fellow. B. A. J. P. is a Gibb Fellow of the CRC.
2 These authors contributed equally to this study.
3 To whom requests for reprints should be addressed, at CRC Human Cancer Genetics Research Group, Cambridge University, Addenbrooke's Hospital, Box 238, Hills Road, Cambridge, CB2 2QQ, United Kingdom. Phone: +44-1223-336900; Fax: +44-1223-336902; E-mail: bajp@mole.bio.cam.ac.uk.
Received 12/ 4/97. Accepted 2/13/98.
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