In this manner, three HPA/PKU mouse models have previously been established; namely, (i) Enu1 (enu1 allele), with the p.V106A-PAH mutation, located in the PAH regulatory domain10; (ii) Enu2 (enu2 allele), with the p.F263S-PAH mutation, located in the catalytic domain10; and (iii) Enu3 (enu3 allele), with a splice site mutation generating frameshifted amino acids and premature termination codon11. This evidence concerns the gene PAH and phenylketonuria.