In mice, null mutations of the breast cancer susceptibility gene Brca1 result in embryonic lethality. In the May 15 Genes & Development, Ludwig et al. describe the generation of a mutant mouse that expresses a truncated Brca1 protein that mimics mutations found in human breast cancer patients (Genes & Development 2001, 15:1188-1193). They used a two-step 'knock-in' targeting strategy to insert a stop codon in Brca1 exon 11. The genetic background of the mice determined the extent of embryonic lethality. Surviving mice homozygous for the truncated Brca1 allele developed tumours at high frequency (about 85%) at around 17 months of age. The tumour spectrum included lymphomas, sarcomas, and carcinomas, and histologically diverse breast carcinomas developed in some mutant mice. The authors speculate that the truncated Brca1 protein plays a role in the late stages of tumour progression.

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