title: Animal models of inherited complement deficiency.
abstract: The initial description of murine strains deficient in complement component C5 has been followed by the recognition in a range of animal species of a variety of natural complement component deficiencies, many of which have been characterized at the molecular level. The use of such species in inflammatory and infectious experimental models has led to significant progress in understanding the role of specific complement factors (and pathways) in disease pathogenesis. Deficiencies of early complement factors are characterized by impairment of immune response, possibly due to defective processing of immune complexes. Complete (but not partial) deficiency of the central component C3 predisposes affected animals to significant risk of infection and renal disease. Studies in species deficient in the terminal pathway component C6 are particularly relevant for investigating the pathogenetic role of the terminal membrane attack complex (MAC), implicating it as a causative agent in diverse inflammatory insults such as reperfusion injury, glomerular damage, and xenograft hyperacute rejection. Further investigations in such naturally deficient strains, added to results derived from studies in knockout animals, are likely to expand our understanding of the role of the activated complement system in experimental inflammatory disease, with significant potential implications for the treatment of human disease.
authors.affiliation: Department of Rheumatology, Nevill Hall Hospital, Brecon Road, Abergavenny, NP7 7EG, UK. lintons@doctors.org.uk
authors.forename: S
authors.initials: S
authors.lastname: Linton
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001424:Bacterial Infections / Q000276:immunology; D017242:Complement Factor H / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D003171:Complement Pathway, Classical / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D008565:Membrane Proteins; D010272:Parasitic Diseases / Q000276:immunology; D011951:Receptors, Complement / Q000172:deficiency / Q000235:genetics / Q000276:immunology
chemical_list: C493495:CFH protein, human; D008565:Membrane Proteins; D011951:Receptors, Complement; C085567:complement C3a receptor; D017242:Complement Factor H; D003165:Complement System Proteins