Deficiency of the mouse complement regulatory protein mCd59b results in spontaneous hemolytic anemia with platelet activation and progressive male infertility.
Basal 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.
Qin
Xuebin
X
Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Krumrei
Nicole
N
Grubissich
Luciano
L
Dobarro
Martin
M
Aktas
Huseyin
H
Perez
Graciela
G
Halperin
Jose A
JA
D000743:Anemia, Hemolytic / Q000097:blood / Q000209:etiology* / Q000276:immunology; D000818:Animals; D018957:CD59 Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007248:Infertility, Male / Q000097:blood / Q000209:etiology* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D015539:Platelet Activation / Q000276:immunology*; D013081:Sperm Motility / Q000276:immunology; D013094:Spermatozoa / Q000002:abnormalities
D018957:CD59 Antigens