Serping1 Knockout mouse models

Serping1, the mouse ortholog of human SERPING1, encodes C1 inhibitor, a heavily glycosylated serpin with a long mucin-like N-terminal domain that inactivates C1r and C1s in the classical pathway, MASP1 and MASP2 in the lectin pathway, and, critically for disease, plasma kallikrein and factor XIIa in the contact system. Loss of one functional allele produces hereditary angioedema type I through low protein levels and type II through dysfunctional reactive center loop variants, and in both cases unrestrained kallikrein liberates bradykinin from high molecular weight kininogen to cause bradykinin B2 receptor dependent vascular leak. Because heterozygous insufficiency drives the human phenotype, heterozygous or hypomorphic knockins recapitulate disease better than complete nulls, which are viable but display constitutive leak, and humanized alleles are needed to test C1 inhibitor concentrates or kallikrein-directed antibodies. Compensation by other serpins is limited, so use extravasation, plasma kallikrein activity, or complement consumption endpoints.

Whole body loss of Serping1 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.