huSLC6A19/Pah-KO Mouse
Product Name
huSLC6A19/Pah-KO Mouse
Product ID
C002115
Strain Name
C57BL/6Cya-Slc6a19tm1(hSLC6A19)Pahem1/Cya
Background
C57BL/6Cya
Status
Citations
0
When using this mouse strain in a publication, please cite “huSLC6A19/Pah-KO Mouse (Catalog C002115) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Standard products are sold as live mice derived from cryorecovery or expansion. Frozen materials are available upon request. Pricing and lead times depend on real-time inventory.
Gene Name
Pah & SLC6A19
Gene Alias
HND, B0AT1
NCBI ID
Chromosome
Chr 10 (Mouse), Chr 5 (Human)
MGI ID
Datasheet
Strain Description
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.
Reference
Jiang Y, Rose AJ, Sijmonsma TP, et al. Mice lacking neutral amino acid transporter B(0)AT1 (Slc6a19) have elevated levels of FGF21 and GLP-1 and improved glycaemic control. Mol Metab. 2015;4(5):406-417. Published 2015 Feb 16.
Bröer S. The role of the neutral amino acid transporter B0AT1 (SLC6A19) in Hartnup disorder and protein nutrition. IUBMB Life. 2009;61(6):591-599. McFadden RG. Collaboration--no other way to go. Can Respir J. 2012;19(5):296-297.
McFadden RG. Collaboration--no other way to go. Can Respir J. 2012;19(5):296-297.
Elhawary NA, AlJahdali IA, Abumansour IS, Elhawary EN, Gaboon N, Dandini M, Madkhali A, Alosaimi W, Alzahrani A, Aljohani F, Melibary EM, Kensara OA. Genetic etiology and clinical challenges of phenylketonuria. Hum Genomics. 2022 Jul 19;16(1):22.
MedlinePlus Genetics. PAH gene. U.S. National Library of Medicine. https://medlineplus.gov/genetics/gene/pah/
Strain Strategy
The huSLC6A19/Pah-KO mouse is a combined genetically modified model obtained by crossing the huSLC6A19 mouse (Catalog No.: C002000) with the Pah-KO mouse (Catalog No.: C001560).
Figure 1. Gene editing strategy of huSLC6A19 mice. The sequences from the start codon to the 3'UTR of the endogenous mouse Slc6a19 gene were replaced with the sequences from the start codon to the 3'UTR of the human SLC6A19 gene. The expression of mouse Slc6a19os may be affected by this KI region.
Figure 2. Gene editing strategy of Pah-KO mice. The Pah gene is located on chromosome 10 in mice, and knocking out exon 3 of the mouse Pah gene using gene editing technology resulted in a strain with a deletion of Pah gene expression.
Application Area
Screening, pharmacodynamic evaluation, safety evaluation, and mechanism-of-action studies of drugs targeting SLC6A19;
Research on phenylketonuria (PKU), amino acid metabolism disorders, and related fields.
Contact Us
Connect with our experts for your custom animal model needs. Please fill out the form below to start a conversation or request a quote.
Cyagen values your privacy. We’d like to keep you informed about our latest offerings and insights. Your preferences:
You may unsubscribe from these communications at any time. See our Privacy Policy for details on opting out and data protection.
By clicking the button below, you consent to allow Cyagen to store and process the personal information submitted in this form to provide you the content requested.