Mice lacking the guanylyl cyclase C receptor are resistant to STa-induced intestinal secretion.
Heat-stable enterotoxin (STa) is an important causative agent of diarrheal disease throughout the world. STa is known to bind specifically to receptors in the intestine, provoking intense intestinal secretion. Binding of STa, or of the mammalian endogenous ligands guanylin and uroguanylin, activates the guanylyl cyclase C receptor (GC-C); the resulting elevation of cGMP levels stimulates chloride secretion via CFTR. We have generated knockout mice which completely lack the GC-C receptor. These mice are viable and show no obvious alteration in intestinal fluidity. However, GC-C null mice are refractory to the secretory action of STa, proving that the GC-C receptor is necessary for the diarrheal response induced by STa.
Mann
E A
EA
VA Medical Center, University of Cincinnati, Ohio 45267, USA.
Jump
M L
ML
Wu
J
J
Yee
E
E
Giannella
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001681:Biological Assay; D015152:Blotting, Northern; D002478:Cells, Cultured; D004351:Drug Resistance; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D006162:Guanylate Cyclase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C034151:heat stable toxin (E coli); D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled