Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice.
To investigate the roles of astroglial cells, we targeted their ablation genetically. Transgenic mice were generated expressing herpes simplex virus thymidine kinase from the mouse glial fibrillary acidic protein (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, causing a fulminating and fatal jejuno-ileitis. This pathology was independent of bacterial overgrowth and was characterized by increased myeloperoxidase 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.
Bush
T G
TG
Medical Research Council Cambridge Centre for Brain Repair, Department of Anatomy, University of Cambridge, United Kingdom.
Savidge
T C
TC
Freeman
T C
TC
Cox
H J
HJ
Campbell
E A
EA
Mucke
L
L
Johnson
M H
MH
Sofroniew
M V
MV
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001253:Astrocytes / Q000502:physiology*; D001930:Brain Injuries; D002478:Cells, Cultured; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology; D003106:Colon / Q000473:pathology; D017615:Enteric Nervous System / Q000473:pathology*; D004751:Enteritis; D015774:Ganciclovir / Q000494:pharmacology; D006471:Gastrointestinal Hemorrhage; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000235:genetics; D007079:Ileitis / Q000473:pathology*; D007082:Ileum / Q000294:innervation; D007421:Intestine, Small / Q000382:microbiology / Q000473:pathology; D007579:Jejunal Diseases / Q000473:pathology*; D007583:Jejunum / Q000294:innervation / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D009195:Peroxidase / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics
D000900:Anti-Bacterial Agents; D005904:Glial Fibrillary Acidic Protein; D009195:Peroxidase; D013937:Thymidine Kinase; D015774:Ganciclovir