Cfd Conditional Knockout mouse models

Complement factor D, also called adipsin, is encoded by mouse Cfd, ortholog of human CFD, and constitutes the rate-limiting protease of the alternative pathway. Factor D is unique among complement proteases in circulating as a mature enzyme rather than a zymogen, held in a self-inhibited conformation by a distorted active site and a blocking self-inhibitory loop that is relieved only upon docking to the exosite presented by factor B once factor B has engaged C3b, an elegant substrate-induced activation that prevents fluid phase proteolysis. It is secreted largely by adipocytes, linking metabolic tissue to complement amplification and insulin secretion biology. Human deficiency causes recurrent Neisseria infection, and mouse nulls lack alternative pathway activity while retaining classical function, with no paralog to compensate. Choose the null or an adipocyte-conditional allele to test tissue source and metabolic crosstalk, and humanized knockins when danicopan class molecules exploiting the self-inhibited pocket are the endpoint.

A floxed Cfd 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.