Sod1 Conditional Knockout mouse models

Cytosolic superoxide detoxification is carried out by Sod1, the mouse ortholog of human SOD1, encoding copper and zinc superoxide dismutase, a beta-barrel homodimer stabilized by an intrasubunit Cys57 to Cys146 disulfide and metallated by the copper chaperone CCS, which dismutates superoxide to hydrogen peroxide and oxygen in cytosol and mitochondrial intermembrane space. More than 180 dominant SOD1 mutations, including G93A, G85R, and A4V, cause ALS1 through gain of toxic function involving misfolding, aberrant metal handling, and aggregation rather than loss of dismutase activity, a distinction confirmed because Sod1 knockout mice do not develop motor neuron disease but instead show distal axonopathy, hearing loss, muscle atrophy, and oxidative damage. Allele design therefore favors patient missense knockins at the endogenous locus over overexpression transgenes when physiologic dosage matters, with humanized alleles required for tofersen-class antisense oligonucleotide testing and conditional nulls reserved for cell-autonomy questions.

A floxed Sod1 allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.