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 were born at the expected ratio from a cross between pIgR+/- mice, indicating that disruption of the pIgR gene in mice is not lethal. pIgR and secretory component proteins were not detected in pIgR-/- mice by Western blot analysis. Moreover, immunohistochemical analysis showed that pIgR protein is 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 remarkable increase in serum IgA concentration and a slight increment of serum IgG and IgE levels, leaving serum IgM level unaltered. In contrast, IgA was much reduced but not negligible in the bile, feces, and intestinal contents of pIgR-/- mice. Additionally, IgA with a molecular mass of 280 kDa preferentially accumulated in the serum of pIgR-/- mice, suggesting that transepithelial transport of dIgA is severely blocked in pIgR-/- mice. These results demonstrate that dIgA is mainly transported by pIgR on the epithelial cells of intestine and hepatocytes, but a small quantity of IgA may be secreted via other pathways.
Shimada
S
S
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Kawaguchi-Miyashita
M
M
Kushiro
A
A
Sato
T
T
Nanno
M
M
Sako
T
T
Matsuoka
Y
Y
Sudo
K
K
Tagawa
Y
Y
Iwakura
Y
Y
Ohwaki
M
M
D000818:Animals; D001646:Bile / Q000737:chemistry; D019281:Dimerization; D005091:Exons / Q000235:genetics; D005803:Genes, Immunoglobulin / Q000235:genetics; D005822:Genetic Vectors / Q000138:chemical synthesis; D017098:IgA Deficiency / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000032:analysis / Q000378:metabolism*; D007419:Intestinal Secretions / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019056:Receptors, Polymeric Immunoglobulin / Q000172:deficiency* / Q000235:genetics*; D011995:Recombination, Genetic; D012635:Secretory Component / Q000032:analysis / Q000378:metabolism; D017384:Sequence Deletion
D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin; D012635:Secretory Component