A targeting vector was designed to insert an ENSMUST00000002487:c.1910T>A mutation (leading to a p.V637E substitution) into exon 18 (ENSMUST00000101497 exon 15). A loxP site, a minigene (cDNA sequence encoding exons 15-18 (last exon) of wild-type Braf splice variant ENSMUST00000101497 with alpha-globin splice acceptor sequences at the 5' end and alpha-globin pol(A) signal sequences at the 3' end), and a loxP site flanked neomycin resistance gene cassette were inserted into intron 17. Upon cre expression, the minigene-STOP-neo cassette is deleted, enabling expression of the mutated sequence. This mutation increases the kinase activity of the protein and is the equivalent of the human c.1799T>A (p.V600E) mutation, the most common oncogenic mutation in BRAF.