A stable liver-specific urate oxidase gene knockout hyperuricemia mouse model finds activated hepatic de novo purine biosynthesis and urate nephropathy.
Biochim Biophys Acta Mol Basis Dis
; 1870(3): 167009, 2024 03.
Article
in En
| MEDLINE
| ID: mdl-38237409
ABSTRACT
Urate oxidase (Uox)-deficient mice could be an optimal animal model to study hyperuricemia and associated disorders. We develop a liver-specific conditional knockout Uox-deficient (UoxCKO) mouse using the Cre/loxP gene targeting system. These UoxCKO mice spontaneously developed hyperuricemia with accumulated serum urate metabolites. Blocking urate degradation, the UoxCKO mice showed significant de novo purine biosynthesis (DNPB) in the liver along with amidophosphoribosyltransferase (Ppat). Pegloticase and allopurinol reversed the elevated serum urate (SU) levels in UoxCKO mice and suppressed the Ppat up-regulation. Although urate nephropathy occurred in 30-week-old UoxCKO mice, 90 % of Uox-deficient mice had a normal lifespan without pronounced urate transport abnormality. Thus, UoxCKO mice are a stable model of human hyperuricemia. Activated DNPB in the UoxCKO mice provides new insights into hyperuricemia, suggesting increased SU influences purine synthesis.
Key words
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1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hyperuricemia
/
Kidney Diseases
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
Year:
2024
Document type:
Article
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