Cfi Conditional Knockout mouse models

Cfi, ortholog of human CFI, encodes complement factor I, the sole protease that irreversibly inactivates deposited C3b and C4b. The secreted two-chain enzyme couples a heavy chain of FIMAC, SRCR, and two LDL receptor class A modules to a chymotrypsin-like serine protease light chain that is unusual in requiring an allosteric partner: catalysis proceeds only when C3b or C4b is engaged with a cofactor such as factor H, membrane cofactor protein CD46, C4b-binding protein, or CR1, which explains both its exceptional specificity and its sequential cleavage of C3b at two arginine sites to yield iC3b and then C3dg. Human deficiency causes secondary C3 depletion with pyogenic infection, and heterozygous mutations predispose to atypical hemolytic uremic syndrome and macular degeneration. Nulls consume C3 spontaneously and lack compensating proteases. Deploy the null for uncontrolled amplification phenotypes, hepatocyte-conditional alleles to test liver source, and humanization when factor I supplementation or cofactor-dependent activity is measured.

Conditional deletion of Cfi 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 Cfi floxed stock yields usable cohorts.