• The PAH enzyme functions in liver as homo-tetramers to hydroxylate phenylalanine (Phe) into tyrosine and requires the co-factor tetrahydrobiopterin for catalysis. Phenylalanine hydroxylase (PAH) deficiency prevents the conversion of Phe to tyrosine. PAH deficiency results in hyperphenylalaninemia (HPA) and irreversible neurological consequences if left untreated.
• The exons 1-13 of mouse Pah gene that encode the full-length protein were knocked out in B-Pah KO mice..
• Pah protein expression was detected in the liver and kidneys of both female and male wild mice and heterozygous mice. Moreover, Pah protein expression of both female and male wild mice was higher than that of heterozygous mice.
• B-Pah KO mice provide a powerful preclinical model for further development of gene and cell biologics to treat phenylketonuria(PKU).
• Application: For example, this product is to add to the experimental tools available for PKU scientists and to advance PKU research.

Gene targeting strategy for B-Pah KO mice. The exons 1-13 of mouse Pah gene that encode the full-length protein were knocked out in B-Pah KO mice.

Western blot analysis of Pah protein expression in heterozygous B-Pah KO mice . Various tissue lysates were collected from wild-type C57BL/6N mice (+/+) and heterozygous B-Pah KO mice (H/+), and then analyzed by western blot with anti-Pah antibody(abcam, ab178430). 40 μg total proteins were loaded for western blotting analysis. Pah protein expression was detected in the liver and kidneys of both female and male wild mice and heterozygous mice. Moreover, Pah protein expression of both female and male wild mice was higher than that of heterozygous mice.

Strain specific analysis of PAH mRNA expression in wild-type C57BL/6JNifdc mice and B-Pah KO mice by RT-PCR. Liver RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-Pah KO mice (-/-), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse Pah primers. Mouse Pah mRNA was exclusively detectable in wild-type mice but not in homozygous B-Pah KO mice.