title: Generation and phenotyping of mCd59a and mCd59b double-knockout mice.
abstract: CD59 is a membrane protein inhibitor of the membrane attack complex (MAC) of complement. Humans express only one, whereas mice express two CD59 genes. We previously reported the targeted deletion of the mCd59b gene in which absence of mCd59b together with an unintended down regulation of mCd59a caused hemolytic anemia with spontaneous platelet activation. To confirm the complement role in the hemolytic anemia caused by abrogation of mCd59 function, we have developed a mCd59a and mCd59b double knock out mice and analyzed its phenotype in complement sufficient and deficient (C3(-/-)). We report here that total abrogation of mCd59 function in mCd59ab(-/-) mice results in complement-mediated hemolytic anemia that is rescued by the deficiency of C3 in compound mCd59ab(-/-)/C3(-/-) mice.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. xuebin_qin@hms.harvard.edu
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qin
authors.forename: Weiguo
authors.initials: W
authors.lastname: Hu
authors.forename: Wenping
authors.initials: W
authors.lastname: Song
authors.forename: Luciano
authors.initials: L
authors.lastname: Grubissich
authors.forename: Xuemei
authors.initials: X
authors.lastname: Hu
authors.forename: Gongxiong
authors.initials: G
authors.lastname: Wu
authors.forename: Sean
authors.initials: S
authors.lastname: Ferris
authors.forename: Martin
authors.initials: M
authors.lastname: Dobarro
authors.forename: Jose A
authors.initials: JA
authors.lastname: Halperin
mesh_terms: D000745:Anemia, Hemolytic, Congenital / Q000235:genetics* / Q000276:immunology; D000818:Animals; D018957:CD59 Antigens / Q000235:genetics* / Q000502:physiology; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology; D003171:Complement Pathway, Classical; D003433:Crosses, Genetic; D005091:Exons / Q000235:genetics; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D055786:Gene Knockout Techniques; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D015539:Platelet Activation; D051381:Rats
chemical_list: D018957:CD59 Antigens; C539311:CD59a protein, mouse; C539312:CD59b protein, mouse; D003176:Complement C3; D015938:Complement Membrane Attack Complex