A loxP site flanked neomycin resistance gene cassette was inserted into intron 11 and a tyrosine codon 487 (TAC) in exon 12 was changed to alanine (GCA) (p.Y487A). Cre-mediated recombination removed the neo cassette. This mutation disrupts the E3 ligase activity without altering binding to MDM4. (J:214218)