Deficiency of the Mouse Complement Regulatory Protein mCd59b Results in Spontaneous Hemolytic Anemia with Platelet Activation and Progressive Male Infertility

AbstractBasal complement activity presents a potential danger for “self” cells that are tightly protected by complement regulators including CD59. Mice express two Cd59 genes (mCd59a and mCd59b); mCd59b has approximately a 6-fold higher specific activity than mCd59a. Consistently, mCd59b knockout mice present a strong phenotype characterized by hemolytic anemia with increased reticulocytes, anisopoikilocytosis, echinocytosis, schistocytosis, free hemoglobin in plasma, hemoglobinuria with hemosiderinuria, and platelet activation. Remarkably, mCd59b−/− males express a progressive loss of fertility associated with immobile dysmorphic and fewer sperm cells after 5 months of age. This work indicates that mCd59b is a key complement regulator in mice and that CD59 is critical in protecting self cells; it also provides a novel model to study complement regulation in human diseases