Look at the effects of knocking out the BRCA 1 gene in mice. Mutations in the BR

Question

Look at the effects of knocking out the BRCA 1 gene in mice. Mutations in the BRCA1 gene result in a greatly increased risk of breast cancer in women with mutations that will develop cancer A very simplified version of the gene is shown below. Draw the targeting construct/vector you would need knockout this gene. a. Exon Exon 2 Exon 3 Ex. b. Unfortunately, when you knock out this gene, you find that homozygous knockout mice die during development. You want to knockout expression of the BRCA1 gene only in mammary tissue. How would you do this? In other words, how can you generate mice that will develop normally, but where you can then eliminate gene expression in one particular tissue? Be sure your explanation includes the two genetically modified mouse strain(s) that you would need to mate.

Explanation / Answer

hereditary breast cancer cases is caused by BRCA1 germline mutations. In this review, we will discuss the insights into BRCA1 functions that we obtained from mouse models with conventional and conditional mutations in Brca1. The most advanced models closely resemble human BRCA1-related breast cancer and may therefore be useful for addressing clinically relevant questions.

Keywords: BRCA1, breast cancer, mouse models, tumour suppressor

Breast cancer is by far the most frequent cancer in women, accounting for over 20% of all cancer cases. Familial breast cancers, including those associated with heterozygous germline mutations in the major susceptibility genes BRCA1 and BRCA2, account for 5–10% of breast cancer cases in the western world. BRCA1 mutation carriers have a lifetime risk of about 80% for developing breast cancer and a 40% lifetime risk for developing ovarian cancer. Most BRCA1-associated tumours show loss of heterozygosity (LOH) at the BRCA1 locus, leading to loss of the wild-type allele, which is consistent with a tumour suppressor function of BRCA

several genetically engineered mouse models have been generated for studying the in vivo functions of BRCA1. Initial studies used conventional knockout mice with germline mutations in the mouse Brca1 gene. These conventional Brca1 mouse mutants have enabled us to learn a lot about the biological roles of BRCA1. Because of the embryonic lethality of homozygous animals carrying two defective Brca1 alleles and the lack of mammary tumour development in heterozygous mice carrying one defective and one wild-type Brca1 allele, these models could not be used to study the role of BRCA1 in tumorigenesis. To overcome these problems, the investigators generated conditional Brca1 knockout mice that enable tissue-specific inactivation of BRCA1

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