MICE DEFICIENT FOR THE COMPLEMENT FACTOR-B DEVELOP AND REPRODUCE NORMALLY

Factor B is an essential component of the complement cascade which for ms the C3 and C5 convertase of the alternative pathway. Factor B cleav age products also function as cofactors in antibody-independent monocy te-mediated cytotoxicity, macrophage spreading, plasminogen activation and proliferation of B lymphocytes. Several healthy kindreds heterozy gous for the factor B null or non-functional allele have been reported but the absence of homozygous factor B deficiency in humans or in ani mals has been speculated to be caused by the lethality of the phenotyp e. Here we report the generation of factor B-deficient mice by gene ta rgeting in vivo. These mice were born at the expected Mendelian ratio and they both develop and breed normally in a conventional animal faci lity. These mice represent a model of complete alternative pathway def iciency. This model enables the dissection of the complement cascade i n vivo and the elucidation of the relative contribution of this comple ment pathway in the various physiological and pathological phenomena a scribed to the complement system.