Three first-generation HPA/PKU mouse models were created through phenotypically driven germline mutagenesis using N-ethyl-N-nitrosourea [2]: (1) Enu1, which carries the p.V106A variant located in the Pah regulatory domain [15]; (2) Enu2, which carries the p.F263S variant located in the catalytic domain sequence of Pah [15]; and (3) Enu3, which has splice site variants that produce frameshift amino acids and early termination codons in Pah [16]. This evidence concerns the gene PAH and phenylketonuria.