Colon water transport in transgenic mice lacking aquaporin-4 water channels

Transgenic null mice were used to test the hypothesis that water channel aq uaporin-4 (AQP4) is involved in colon water transport and fecal dehydration . AQP4 was immunolocalized to the basolateral membrane of colonic surface e pithelium of wild-type (+/+) mice and was absent in AQP4 null (-/-) mice. T he transepithelial osmotic water permeability coefficient (P-f) of in vivo perfused colon of +/+ mice, measured using the volume marker C-14-labeled p olyethylene glycol, was 0.016 +/- 0.002 cm/s. P-f of proximal colon was gre ater than that of distal colon (0.020 +/- 0.004 vs. 0.009 +/- 0.003 cm/s, P < 0.01). P-f was significantly lower in +/+ mice when measured in full-len gth colon (0.009 +/- 0.002 cm/s, P < 0.05) and proximal colon (0.013 +/- 0. 002 cm/s, P < 0.05) but not in distal colon. There was no difference in wat er content of cecal stool from +/+ vs. -/- mice (0.80 +/- 0.01 vs. 0.81 +/- 0.01), but there was a slightly higher water content in defecated stool fr om +/+ mice (0.68 +/- 0.01 vs. 0.65 +/- 0.01, P < 0.05). Despite the differ ences in water permeability with AQP4 deletion, theophylline- induced secre tion was not impaired (50 +/-9 vs. 51 +/- 8 mu l . min(-1) . g(-1)). These results provide evidence that transcellular water transport through AQP4 wa ter channels in colonic epithelium facilitates transepithelial osmotic wate r permeability but has little or no effect on colonic fluid secretion or fe cal dehydration.