| Abnormalities of the enteric nervous system in heterozygous endothelin B receptor deficient (spotting lethal) rats resembling intestinal neuronal dysplasia. | |
| | |
MedLine Citation:
|
PMID: 12171966 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: A homozygous mutation of the endothelin B receptor (EDNRB) gene in spotting lethal (sl/sl) rats leads to Hirschsprung's disease (HSCR) with long segmented aganglionosis. However, the effects on the development of the enteric nervous system (ENS) promoted by a heterozygous mutation of the EDNRB gene are not known. The present study aimed to describe and morphometrically assess the phenotypic abnormalities of the ENS in heterozygous (+/sl) EDNRB deficient rats in comparison with homozygous (sl/sl) EDNRB deficient and wild-type (+/+) rats. METHODS: The distal small intestine, caecum, and colon were obtained from sl/sl, +/sl, and +/+ rats. To demonstrate the three dimensional organisation of the ENS, the intestinal wall was microdissected into wholemounts and incubated against the pan-neuronal marker protein gene product 9.5. Assessment of the ENS included morphometric quantification of ganglionic size and density, the number of nerve cells per ganglia, and the diameter of nerve fibre strands within both the myenteric and submucous plexus. RESULTS: Sl/sl rats were characterised by complete aganglionosis resembling the same histopathological features observed in patients with HSCR. +/sl rats revealed more subtle abnormalities of the ENS: the submucous plexus was characterised by a significantly increased ganglionic size and density, and the presence of hypertrophied nerve fibre strands. Morphometric evaluation of the myenteric plexus did not show statistically significant differences between +/sl and +/+ rats. CONCLUSIONS: In contrast with sl/sl rats, +/sl rats display non-aganglionated malformations of the ENS. Interestingly, these innervational abnormalities resemble the histopathological criteria for intestinal neuronal dysplasia (IND). Although IND has been described in several intestinal motility disorders, the concept of a clearly defined clinical-histopathological entity is still controversially discussed. The present findings support the concept of IND based on clearly defined morphological criteria suggesting a genetic link, and thus may provide a model for human IND. Furthermore, the data underline the critical role of the "gene dose" for the phenotypic effects promoted by the EDNRB/EDN3 system and confirm that the development of the ENS is not an "all or none" phenomenon. |
| | |
Authors:
|
G B T von Boyen; H-J Krammer; A Süss; C Dembowski; H Ehrenreich; T Wedel |
Related Documents
:
|
22523286 - Effects of culture supernatant from lactobacillus pentosus strain s-pt84 on autonomic n... 10440486 - Toluene and styrene intoxication route in the rat cochlea. 21476206 - Effect of acupuncture on rats with acute gouty arthritis inflammation: a metabonomic me... 18037506 - Strain-specific susceptibility for neurodegeneration in a rat model of autoimmune optic... 9933756 - Effect of ginsenoside-rd in cephaloridine-induced renal disorder. 21994856 - Unique properties of hepatocarcinogenesis-resistant drh rat hepatocytes linked or not l... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Gut Volume: 51 ISSN: 0017-5749 ISO Abbreviation: Gut Publication Date: 2002 Sep |
Date Detail:
|
Created Date: 2002-08-12 Completed Date: 2002-10-02 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 2985108R Medline TA: Gut Country: England |
Other Details:
|
Languages: eng Pagination: 414-9 Citation Subset: AIM; IM |
Affiliation:
|
Department of Medicine II (Gastroenterology), University Hospital of Heidelberg at Mannheim, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cecum / innervation Colon / innervation Enteric Nervous System / abnormalities*, pathology Heterozygote Ileum / innervation Intestinal Diseases / genetics*, pathology Intestine, Small / innervation Peripheral Nervous System Diseases / genetics*, pathology Phenotype Rats Rats, Wistar Receptor, Endothelin B Receptors, Endothelin / deficiency, genetics* |
| Chemical | |
Reg. No./Substance:
|
0/Receptor, Endothelin B; 0/Receptors, Endothelin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prognosis in post-infective irritable bowel syndrome: a six year follow up study.
Next Document: Explaining variation in familial adenomatous polyposis: relationship between genotype and phenotype ...