Uqcrc2 Knockout mouse models

Encoding core protein 2 of the cytochrome bc1 complex, Uqcrc2 is the mouse ortholog of human UQCRC2 and pairs with core protein 1 in a mitochondrial processing peptidase-like heterodimer that projects into the matrix and forms the scaffold stabilizing the catalytic subunits of complex III, including cytochrome b, cytochrome c1 and the Rieske iron-sulfur protein. Loss of this scaffold prevents productive holoenzyme assembly and lowers ubiquinol to cytochrome c oxidoreductase activity, and recessive human mutations cause complex III deficiency presenting with recurrent metabolic crises, hypoglycemia, hyperammonemia and lactic acidosis. Because the phenotype is dose sensitive, a patient-matched missense knockin preserving partial assembly usually models the human disease more faithfully than deletion, while a floxed conditional null establishes where complex III capacity is limiting, with hepatic and neuronal drivers highest yield given the crisis phenotype. Core protein 1 does not compensate. Match allele class to assembly profiling, respirometry, fasting challenge and ammonia and lactate endpoints.

A conventional Uqcrc2 knockout removes gene function in all cells that inherit the allele. It is a proven first pass for target validation when redundancy is low.