Further characterization of reproductive abnormalities in mCd59b knockout mice: a potential new function of mCd59 in male reproduction.
CD59 is a GPI-linked membrane protein that inhibits formation of the membrane attack complex of complement. We reported recently that mice have two CD59 genes (termed mCd59a and mCd59b), and that the targeted deletion of mCd59b (mCd59b-/-) results in spontaneous hemolytic anemia and progressive loss of male fertility. Further studies of the reproductive abnormalities in mCd59b-/- mice reported in this study revealed the presence of abnormal multinucleated cells and increased apoptotic cells within the walls of the seminiferous tubules, and a decrease in the number, motility, and viability of sperm associated with a significant increase in abnormal sperm morphologies. Both the capacitation-associated tyrosine phosphorylation and the ionophore-induced acrosome reaction as well as luteinizing hormone, follicle-stimulating hormone, and testosterone serum levels were similar in mCd59b-/- and mCd59b+/+. Surprisingly, the functional deficiency of the complement protein C3 did not rescue the abnormal reproductive phenotype of mCd59b-/-, although it was efficient in rescuing their hemolytic anemia. These results indicate that the male reproductive abnormalities in mCd59b-/- are complement-independent, and that mCd59 may have a novel function in spermatogenesis that is most likely unrelated to its function as an inhibitor of membrane attack complex formation.
Qin
Xuebin
X
Department of Medicine, Division of Hematology and Oncology, Brigham and Women's Hospital, Boston, MA 02115, USA. xuebin_qin@hms.harvard.edu
Dobarro
Martin
M
Bedford
Sylvia J
SJ
Ferris
Sean
S
Miranda
Patricia V
PV
Song
Wenping
W
Bronson
Roderick T
RT
Visconti
Pablo E
PE
Halperin
Jose A
JA
D000743:Anemia, Hemolytic / Q000235:genetics / Q000276:immunology; D000818:Animals; D017209:Apoptosis; D018957:CD59 Antigens / Q000235:genetics / Q000502:physiology*; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007248:Infertility, Male / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D012098:Reproduction / Q000276:immunology*; D013075:Sperm Capacitation / Q000276:immunology; D013094:Spermatozoa / Q000002:abnormalities; D013737:Testis / Q000276:immunology / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
D018957:CD59 Antigens; D003176:Complement C3; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D014443:Tyrosine