Isolation, partial characterization, and localization of a rat renal tubular glycoprotein antigen. Antibody-induced birth defects.

Abstract

A glycoprotein with an apparent 340,000 mol wt (gp 340K) was isolated from rat kidney saline-soluble extract by ammonium sulfate precipitation, DE 52 ion-exchange cellulose chromatography, concanavalin A affinity column, Sephacryl S-300 gel filtration, and discontinuous polyacrylamide gel electrophoresis (PAGE). The relative purity of gp 340K was examined by double immunodiffusion analysis, disc PAGE, and immunoelectrophoresis. Injection of rabbit gp 340K antiserum into pregnant rats during the organogenetic period induced abnormal embryonic development, fetal growth retardation, and embryonic death. Antiserum against the immunocomplexes isolated by immobilized protein A also produced the same embryotoxic effects. The biologic effects of the antisera appeared to be dose dependent. Defects such as anophthalmia, hydrocephaly, exencephaly, cleft palate, cleft lip, and some cardiovascular anomalies were observed. The most frequently observed anomaly was anophthalmia. Immunofluorescent localization studies indicated that gp 340K antibodies localized in vivo in the visceral yolk-sac endodermal cells and the embryonic endoderm. In vitro immunofluorescent localization studies revealed that gp 340K was a component of the renal tubular cells that cross-reacted with antigen in the visceral yolk-sac endodermal cells and embryonic endoderm. The underlying mechanism whereby gp 340K antibodies induce birth defects is not known. Three hypotheses were discussed.