Cfh Conditional Knockout mouse models

Cfh, ortholog of human CFH, encodes factor H, the principal soluble regulator restraining alternative pathway amplification on host surfaces. Its twenty complement control protein modules are functionally partitioned: CCP1 to CCP4 accelerate decay of C3bBb and serve as cofactor for factor I cleavage of C3b, while CCP19 and CCP20 read host surface markers, binding sialic acid, glycosaminoglycans, and C3d simultaneously to localize regulation. Loss of function causes uncontrolled fluid phase C3 consumption, and mouse Cfh nulls develop spontaneous C3 glomerulopathy with dense intramembranous deposits, making this one of few complement models with autonomous renal pathology. Human disease splits sharply by domain: CCP20 mutations and anti-factor H autoantibodies cause atypical hemolytic uremic syndrome, whereas the CCP7 Y402H variant drives age-related macular degeneration. Match allele to question using the null for C3 glomerulopathy, domain-specific knockins for surface recognition, and humanization or Y402H equivalents for ocular endpoints.

A floxed Cfh 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.