DEPLETION OF THE ENTERIC NERVOUS-SYSTEM BY GENE TARGETING RESULTS IN HEMORRHAGIC NECROSIS OF THE ILEUM

To investigate the roles of astroglial cells, we targeted their ablati on genetically. Transgenic mice were generated expressing herpes simpl ex virus thymidine kinase from the mouse glial fibrillary acidic prote in (GFAP) promoter. In adult transgenic mice, 2 weeks of subcutaneous treatment with the antiviral agent ganciclovir preferentially ablated transgene-expressing, GFAP-positive glia from the jejunum and ileum, c ausing a fulminating and fatal jejuno-ileitis. This pathology was inde pendent of bacterial overgrowth and was characterized by increased mye loperoxidase activity, moderate degeneration of myenteric neurons, and intraluminal hemorrhage. These findings demonstrate that enteric glia play an essential role in maintaining the integrity of the bowel and suggest that their loss or dysfunction may contribute to the cellular mechanisms of inflammatory bowel disease.