Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA

We generated mouse lacking exon 2 of polymeric Ig receptor (pIgR) gene by a gene-targeting strategy (pIgR-deficient mouse; pIgR(-/-) mouse) to define the physiological role of pIgR in the transcytosis of Igs. pIgR(-/-) mice w ere born at the expected ratio from a cross between pIgR(+/-) mice, indicat ing that disruption of the pIgR gene in mice is not lethal, pIgR and secret ory component proteins were not detected in pIgR(-/-) mice by Western blot analysis. Moreover, immunohistochemical analysis showed that pIgR protein i s not expressed in jejunal and colonic epithelial cells of pIgR(-/-) mice, whereas IgA(+) cells are present in the intestinal mucosa of pIgR(-/-) mice as well as wild-type littermates, Disruption of the pIgR gene caused a rem arkable increase in serum IgA concentration and a slight increment of serum IgG and IgE levels, leaving serum IgM level unaltered. In contrast, IgA wa s much reduced but not negligible in the bile, feces, and intestinal conten ts of pIgR(-/-) mice. Additionally, IgA with a molecular mass of 280 kDa pr eferentially accumulated in the serum of pIgR(-/-) mice, suggesting that tr ansepithelial transport of dIgA is severely blocked in pIgR(-/-) mice, Thes e results demonstrate that dIgA is mainly transported by pIgR on the epithe lial cells of intestine and hepatocytes, but a small quantity of IgA may be secreted via other pathways.