B-raf/loxp-flanked Mutant Mouse

Tech ID: 20279 / UC Case 2006-215-0

Background

B-raf is a member of the Raf family of intracellular signaling proteins, which also include Raf-1 and A-raf. Members of this family are involved in the all-important cellular signaling mechanism known as the Ras/Raf/MEK/ERK/MAPK signaling pathway. This ubiquitous pathway relays signals from outside the cell into the cells nucleus, regulating activities such as gene expression, differentiation, cell division, cell survival and cell death. B-raf regulates vital functions in the brain, testes, skin and bone marrow, and mutations in B-raf are found in malignant melanoma, certain types of thyroid and ovarian cancers, and sporadic types of colon cancers. Up to 6% of all human malignancies may harbor this mutation. Most recently, Sorafenib (Nexavar), which inhibits raf as well as a whole host of other signaling proteins, has been approved by the FDA for the treatment of advanced cancer of the kidney (clear-cell renal cell carcinoma).

Innovation

UCLA researchers have made a B-raf/loxP-flanked transgenic mouse. Flanking the B-raf gene with the loxP sequence allows targeted excision of the B-raf gene only when the cell expresses the protein Cre. This allows selective deletion of B-raf in a cell or tissue-specific manner and in a time or developmentally-specific manner as well.

Applications

  • Cancer research involving the Ras/Raf/MEK/ERK/MAPK signaling pathways
  • Research into learning and memory, and hematopoiesis and myelopoiesis

Advantages

  • Uses proven Cre/LoxP DNA recombination technology for targeted gene excision
  • Unlike knockout mutants with global B-raf deficiency, B-raf/loxP sequence allows deletion of the B-raf gene in a cell or tissue-specific manner
  • Unlike knockout mutants, B-raf/loxP sequence allows deletion of the B-raf gene in a time or developmentally-specific manner, such as after tumorigenesis or transformation
  • Allows functional testing in specific cell types without the confounding effects of deleting B-raf in unknown or unrelated cells and tissues

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Inventors

  • Silva, Alcino J.

Other Information

Keywords

research tools therapeutics, mouse model, mice, ERK, cancer, conditional, hematopoiesis, myelopoiesis, learning and memory

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