Pah KO Mouse

Phenylalanine hydroxylase (PAH) is a member of the biotin-dependent aromatic amino acid hydroxylase protein family encoded by the PAH gene. The main function of PAH is to hydroxylate phenylalanine (Phe) into tyrosine (Tyr), a crucial step in phenylalanine catabolic metabolism. Lack of PAH activity can lead to the autosomal recessive inherited disorder phenylketonuria (PKU), also known as PAH deficiency. PKU is a congenital disease caused by pathogenic variants in the PAH gene and belongs to the group of amino acid metabolic disorders. Patients with PKU excrete large amounts of phenylketones and other metabolites in their urine. In PKU patients, deficiency of the PAH enzyme results in elevated blood phenylalanine (Phe) levels, leading to brain dysfunction. Untreated PKU patients may experience severe and irreversible intellectual disabilities, seizures, behavioral disturbances, microcephaly, epilepsy, psychological symptoms, and generalized hypopigmentation of the skin (including hair and eyes). Approximately 1 in 24,000 individuals is affected by PKU ^[1-2].

The Pah KO mice is a phenylketonuria (PKU) disease model generated by knocking out the Pah gene in mice using gene editing techniques. In this model, both Pah mRNA and PAH protein expression are completely absent, leading to PKU-related phenotypes associated with impaired phenylalanine (Phe) catabolic metabolism. As blood Phe levels rise and Tyr levels decrease in the mouse, the pigmentation of their fur gradually fades, and by 8 weeks of age, their fur color becomes entirely brown. Consequently, Pah KO mice serve as valuable tools for studying the genetic mechanisms of PKU in humans and for the preclinical evaluation of therapeutic drugs.