C1q knock-out mice for the study of complement deficiency in autoimmune disease

In humans, homozygous deficiency of the first component of the classical pa thway of complement, C1q, is a powerful disease susceptibility factor for t he development of systemic lupus erythematosus (SLE). This strong associati on indicates that a functional activity of C1q protects from the developmen t of SLE. Studies in vitro have shown that C1q can bind apoptotic keratinoc ytes suggesting that it may have an important role in the clearance of apop totic cells. C1q-deficient mice, generated by gene targeting, showed an inc reased mortality and 25% of the mice had histological evidence of glomerulo nephritis characterised by multiple apoptotic cell bodies and immune deposi ts, assessed by immunofluorescence and electron microscopy. These observati ons are compatible with the hypothesis that C1q deficiency causes autoimmun ity by an impaired clearance of apoptotic cells.