CRISPR/Cas9 Mediated Deletion of the Uox Gene Generates a Mouse Model of Hyperuricemia with Multiple Complications.
J Cardiovasc Transl Res
; 2024 Jun 10.
Article
de En
| MEDLINE
| ID: mdl-38856882
ABSTRACT
Hyperuricemia is a common metabolic disorder with severe complications. We aimed to develop a mouse model for spontaneous hyperuricemia. Uox-/- mouse model was generated on C57BL/6J background by deleting exon 2-4 of Uox using the CRISPR/Cas9 system. The prototypic Uox -/-mice had 5.5-fold increased serum uric acid (1351.04±276.58µmol/L) as compared to the wild type mice (P<0.0001), but died by 4 weeks. After allopurinol (3ug/g) intervention, they all survived > 8 weeks. The serum uric acid was 612.55±146.98µmol/L in the 8-week-old allopurinol-rescued Uox -/-mice, which manifested multiple complications including severe renal insufficiency, hypertension, left ventricular remodeling and systolic dysfunction, aortic endothelial dysfunction, hepatic steatosis and elevated liver enzymes, as well as hyperglycemia and hypercholesteremia. The present Uox-/- mice developed spontaneous hyperuricemia complicated with urate nephropathy, cardiovascular disease and cardiometabolic disorders, and may provide a novel tool to study hyperuricemia associated early-onset cardiovascular disorders in human.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
J Cardiovasc Transl Res
Sujet du journal:
ANGIOLOGIA
/
CARDIOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine