ROLE OF GENDER AND STRAIN IN VOMITOXIN-INDUCED DYSREGULATION OF IGA PRODUCTION AND IGA NEPHROPATHY IN THE MOUSE

Prolonged dietary exposure of female B6C3F1 mice to the trichothecene vomitoxin results in hyperproduction of immunoglobulin A (IgA) with a concurrent immunopathology that mimics human IgA nephropathy. To asses s the role of gender and strain in the mouse model, semipurified AIN-7 6A diet containing 25 ppm vomitoxin was fed to B6C3F1 male mice and to B6C3F1, BAIBlc, C3H/HeN, C3H/HeJ and C57BL/6 female mice for 8 wk, an d immunopathologic indicators of IgA nephropathy were compared to mice fed clean diet. At the cessation of the experiment all treatment grou ps weighed less than respective controls. Serum IgA was increased in m ale and female B6C3F7 mice as well as in C3H/ Hel, C57BU6, and BALB/c female mice compared to corresponding controls. Serum IgA levels were two- to sixfold higher in B6C3F1 male treatment animals compared to fe male treatment groups from all strains. In contrast, at wk 8 serum IgC levels were unaffected or decreased, and serum IgM was decreased in a ll groups at wk 8. There was a bend toward increased IgA production by Peyer's patch (PP) lymphocytes isolated from treatment mice as compar ed to controls in all groups except the C3H/HeJ mice. Notably, IgA lev els were 18-fold higher in B6C3F1 male treatment PP cultures than in B 6C3F1 female treatment cultures. Hematuria was significantly greater i n treatment mice than respective controls at both wk 4 and 8. Increase d mesangial IgA deposition was also detectable in all treatment groups except the C57BU6 mouse. The results suggested that the male B6C3F1 m ouse and the five strains of female mice exhibited many of the immunop athologic effects found in IgA nephropathy and that IgA elevation was more marked in male B6C3F1 than female B6C3F7 mice.