Antibody induced injury to podocytes with proteinuria and foot process swelling in a transgenic (T16) mouse

T16 mice contain a human 3' untranslated sequence of the Thy 1.1 gene. Unli ke normal mice they express Thy 1.1 protein on the podocytes which was immu ne-localized to podocyte apical and basal plasma membranes and filtration s lit. When monoclonal anti-Thy 1.1 antibody (OX7) was injected in nonprotein uric heterozygous mice there was rapid podocyte foot process swelling and p roteinuria. Immunofluorescence showed granular glomerular OX7 binding at on e hour. Progressive loss of pedicels occurred with 17.9 +/- 2.5, 14.4 +/- 1 .1 and 10.5 +/- 3.5 per 10 nm glomerular basement membrane (GBM) remaining 1, 6 and 24 hours, respectively, after 1 mg OX7, vs 32.2 +/- 2.0 in T16 mic e given saline. Twenty-four hour proteinuria was OX7 dose-dependent, peaked at 1-3 days and reduced to near basal levels 9-11 days thereafter. Protein uria was nonselective except at very low doses (0.1 mg OX7) where microalbu minuria was seen. F(ab')(2) OX7 administration also caused proteinuria in T 16 mice. One milligram F(ab')(1) OX7 caused diffuse foot process swelling w ithout manifest proteinuria in T16 mice. Anti-Thy 1.1 IgM monoclonal antibo dy did not produce the effects of OX7 in T16 mice. Foot process swelling wa s not modified by histamine or 5-hydroxytryptamine antagonists. OX7 did not cause complement activation or leucocyte infiltration, hence glomerular in jury appeared to be mediated directly by the antibody.