B6-hURAT1 Mice

Catalog Number: C001704

Strain Name: C57BL/6NCya-Slc22a12tm1(hSLC22A12)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Heterozygote x Heterozygote

 

Strain Description

The solute carrier family 22 member 12 gene ( SLC22A12) encodes the Urate Transporter 1 (URAT1), a critical transmembrane protein localized to the apical membrane of renal proximal tubule epithelial cells [1]. As the primary mediator of urate reabsorption from the glomerular filtrate, URAT1 plays a pivotal role in maintaining systemic urate homeostasis, a process essential for preventing hyperuricemia and its associated pathologies [2]. Genetic studies have identified numerous variants within SLC22A12 that are strongly linked to renal hypouricemia, characterized by impaired urate reabsorption and an increased risk of exercise-induced acute kidney injury [3]. Furthermore, polymorphisms in SLC22A12 influence the efficacy of uricosuric agents, highlighting its clinical relevance in the management of gout, a common inflammatory arthritis resulting from urate crystal deposition [4]. The functional importance of URAT1 underscores SLC22A12 as a key genetic determinant of urate metabolism and a significant factor in kidney health and disease.

B6-hURAT1 mice are humanized models in which the sequences from ~5 kb upstream of exon 1 to exon 10 of the mouse Slc22a12 gene were replaced with the sequences from ~5 kb upstream of exon 1 to exon 10 of the human SLC22A12 gene. This model can be used to study the pathological mechanisms and therapeutic methods of renal hypouricemia, gout, and other uric acid metabolism-related diseases, as well as the screening and development of URAT1-targeted drugs, and preclinical efficacy and safety evaluations.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hURAT1 mice. The sequences from ~5 kb upstream of exon 1 to exon 10 of the mouse Slc22a12 gene will be replaced with the sequences from ~5 kb upstream of exon 1 to exon 10 of the human SLC22A12 gene.

 

Application

  • Screening, development, and preclinical efficacy evaluation of URAT1-targeted drugs;
  • Study of pathological mechanisms and therapeutic methods for renal hypouricemia, gout, and other uric acid metabolism-related diseases.

 

References
[1]Hou Z, Ma A, Mao J, Song D, Zhao X. Overview of the pharmacokinetics and pharmacodynamics of URAT1 inhibitors for the treatment of hyperuricemia and gout. Expert Opin Drug Metab Toxicol. 2023 Dec;19(12):895-909.
[2]Yang B, Xin M, Liang S, Xu X, Cai T, Dong L, Wang C, Wang M, Cui Y, Song X, Sun J, Sun W. New insight into the management of renal excretion and hyperuricemia: Potential therapeutic strategies with natural bioactive compounds. Front Pharmacol. 2022 Nov 22;13:1026246.
[3]Wu L, Fan Y, Wang Y, Li Z, Mao D, Zhuang W. The impact of an URAT1 polymorphism on the losartan treatment of hypertension and hyperuricemia. J Clin Lab Anal. 2021 Oct;35(10):e23949.
[4]Fan J, Xie W, Ke H, Zhang J, Wang J, Wang H, Guo N, Bai Y, Lei X. Structural Basis for Inhibition of Urate Reabsorption in URAT1. JACS Au. 2025;5(3):1308-1319.