huSLC6A19/Pah-KO Mouse

SLC6A19 (solute carrier family 6 member 19) encodes the neutral amino acid transporter B⁰AT1, a sodium-dependent amino acid transporter mainly expressed in the brush border of the small intestine and epithelial cells of the renal proximal tubule. It is responsible for the intestinal absorption and renal tubular reabsorption of dietary neutral amino acids and plays an important role in maintaining amino acid homeostasis and protein nutrition ^[1-2]. Substrates of SLC6A19 include multiple neutral amino acids such as alanine, serine, leucine, and tryptophan. Dysfunction of SLC6A19 can lead to Hartnup disease, characterized by impaired absorption and reabsorption of neutral amino acids, and some patients may present with niacin deficiency-related skin and neurological symptoms ^[2]. In addition to maintaining nutrient utilization, SLC6A19 also participates in regulating nutrient sensing and energy metabolism. Studies have found that Slc6a19 knockout mice exhibit phenotypes such as altered amino acid homeostasis, elevated FGF21 levels, and improved glucose regulation, suggesting that this transporter may be involved in systemic metabolic regulation by affecting amino acid supply and metabolic signaling ^[3].

Phenylalanine hydroxylase (PAH) is a member of the biopterin-dependent aromatic amino acid hydroxylase protein family, encoded by the PAH gene. The primary function of PAH is to hydroxylate phenylalanine (Phe) to tyrosine (Tyr), a key step in phenylalanine catabolism. Deficiency of PAH activity results in phenylketonuria (PKU), an autosomal recessive genetic disorder also known as PAH deficiency. PKU is a congenital disease caused by pathogenic variants in the PAH gene and belongs to amino acid metabolism disorders. It is named because patients excrete large amounts of phenylpyruvic acid and other metabolites in the urine. In patients with PKU, the lack of PAH enzyme leads to excessively high concentrations of phenylalanine (Phe) in the blood, which in turn causes brain dysfunction. Untreated patients with PKU may develop severe and irreversible intellectual disability, epilepsy, behavioral disorders, acquired microcephaly, seizures, psychological symptoms, and hypopigmentation of the skin throughout the body, including hair and eyes. Approximately 1 in every 24,000 individuals is affected by PKU ^[4-5].

The huSLC6A19/Pah-KO mouse is a combined genetically modified model obtained by crossing huSLC6A19 mice (catalog No.: C002000) with Pah-KO mice (catalog No.: C001560). The huSLC6A19/Pah-KO mouse can be used for screening, pharmacodynamic evaluation, safety evaluation, and mechanism studies of drugs targeting SLC6A19. This model can also be used for research on phenylketonuria (PKU), amino acid metabolic disorders, and related studies, providing a preclinical research tool for exploring the role of targeted SLC6A19 intervention in the context of relevant diseases.