Abnormal embryonic development induced by antibodies to rat visceral yolk-sac endoderm: isolation of the antigen and localization to microvillar membrane.
An antigenic substance was isolated from rat visceral yolk-sac endoderm of the 18th-20th days of gestation by extraction with the nonionic detergent Nonidet P-40, Sephacryl S-300 gel filtration, and Ricinus communis agglutinin affinity chromatography. The rabbit antiserum directed against this antigenic substance when injected into pregnant rats during the period of organogenesis caused abnormal embryonic development, fetal growth retardation, and embryonic death. Ouchterlony gel diffusion analysis demonstrated that the antiserum formed one immunoprecipitin band against the crude detergent extract and a complete identity between the present visceral yolk-sac antigen and the renal glycoprotein antigen previously isolated (C. C. K. Leung, (1982) J. Exp. Med. 156, 372-384). The antigen eluted from the antibody affinity column appeared to consist of two major peptides of 60 and 30 kDa when analyzed by SDS-polyacrylamide gel electrophoresis. Indirect immunofluorescent and immunoperoxidase localization studies at the light microscopic level demonstrated that both rat renal proximal tubule and embryonic visceral yolk-sac endoderm at various gestational stages (including the organogenetic period) shared the same antigen. Indirect immunoperoxidase localization studies at the electron microscopic level demonstrated that the antigen was a part of (or associated with) the microvillar membrane and membrane invaginations at the base of the microvilli of the renal proximal tubule and visceral yolk-sac endoderm. In vivo immunoperoxidase localization studies demonstrated that the teratogenic antibodies localized within the large phagolysosomes and the apical vesicles of the visceral yolk-sac endoderm. It is postulated that visceral yolk-sac pathology was induced by the antibodies.
D000818:Animals; D000941:Antigens / Q000302:isolation & purification; D002462:Cell Membrane / Q000032:analysis / Q000276:immunology; D004707:Endoderm / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000302:isolation & purification; D008871:Microvilli / Q000032:analysis / Q000276:immunology*; D008970:Molecular Weight; D011247:Pregnancy; D051381:Rats / Q000196:embryology*; D013723:Teratogens; D015017:Yolk Sac / Q000276:immunology*
D000941:Antigens; D006023:Glycoproteins; D013723:Teratogens