Ndufs2 Conditional Knockout mouse models

Encoding the mouse ortholog of human NDUFS2, Ndufs2 specifies the 49 kDa core subunit that, together with NDUFS7, NDUFS3 and ND1, builds the quinone-binding chamber of complex I, shaping the terminal N2 cluster environment and coupling quinone reduction to the conformational changes that drive proton translocation in the membrane arm. Biallelic human variants cause Leigh syndrome, hypertrophic cardiomyopathy and optic atrophy with isolated complex I deficiency, and structural work shows that Q-site mutations can uncouple electron transfer from pumping rather than simply reducing enzyme amount. That mechanism argues for patient missense knockins when the goal is to model partial, uncoupled activity, and for conditional nulls with cardiomyocyte, neuronal or retinal Cre when the question is tissue tolerance of complex I loss, since a germline null is not viable. No paralog substitutes for a core subunit. Choose endpoints separating coupling from capacity, including proton pumping and membrane potential, quinone site inhibitor sensitivity, respirometry, echocardiography, and retinal ganglion cell quantification.

Conditional deletion of Ndufs2 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Ndufs2 floxed stock yields usable cohorts.