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The targeting vector is designed to insert a cassette containing floxed exons 15-34 and a mutated endogenous exon 15 downstream of the cassette. Specifically, the vector included, from 5' to 3', a loxP site, splice acceptor, cDNA encoding exons 15-34, a STOP cassette, a PGK-neo cassette, and a second loxP site downstream of endogenous exon 14. Downstream of the cassette, endogenous exon 15 was modified to harbor a Chr. 7: 74146970 T to A substitution, resulting in a leucine to histidine mutation (L424H), identified as the most frequent mutation in human thymic epithelial tumors (TETs). (J:101977)