Ndufs7 Knockout mouse models

Ndufs7, ortholog of human NDUFS7, encodes the PSST core subunit of complex I, which coordinates the terminal [4Fe-4S] cluster N2 and, together with NDUFS2, NDUFS8 and NDUFS3, forms the walls of the ubiquinone-binding channel where electron transfer is coupled to proton pumping. Because N2 sits immediately upstream of quinone reduction, missense substitutions near cluster-ligating cysteines slow turnover and uncouple electron flow from proton translocation, generating the Leigh syndrome and isolated complex I deficiency phenotypes seen in patients. Complete loss of a core catalytic subunit is expected to be developmentally catastrophic, so a conditional floxed allele is the practical route to tissue-restricted ablation, while a residue-matched knockin retains partial activity and models the actual clinical hypomorphic state. No paralog substitutes for a core subunit. Select the knockin for redox and proton-pumping kinetics, and the conditional null with a region-specific Cre for neuropathology and lesion progression.

Whole body loss of Ndufs7 gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.