PUBLICATION
Adult zebrafish intestine resection: a novel model of Short Bowel Syndrome, adaptation, and intestinal stem cell regeneration
- Authors
- Schall, K.A., Holoyda, K.A., Grant, C.N., Levin, D.E., Torres, E.R., Maxwell, A., Pollack, H.A., Moats, R.A., Frey, M.R., Darehzereshki, A., Al Alam, D., Lien, C.E., Grikscheit, T.C.
- ID
- ZDB-PUB-150620-5
- Date
- 2015
- Source
- American journal of physiology. Gastrointestinal and liver physiology 309(3): G135-45 (Journal)
- Registered Authors
- Keywords
- IGF, EGF, Short Bowel Syndrome, adaptation, intestinal failure, intestine stem cell
- MeSH Terms
-
- Adaptation, Biological/physiology*
- Animals
- Antimetabolites/pharmacology
- Bromodeoxyuridine/pharmacology
- Cell Proliferation
- Digestive System Surgical Procedures/methods
- Disease Models, Animal
- Humans
- Insulin-Like Growth Factor I/metabolism
- Intestinal Mucosa/pathology
- Intestines*/pathology
- Intestines*/physiopathology
- Intestines*/surgery
- Male
- Short Bowel Syndrome/metabolism*
- Stem Cells/physiology
- Weight Loss
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 26089336 Full text @ Am. J. Physiol. Gastrointest. Liver Physiol.
Citation
Schall, K.A., Holoyda, K.A., Grant, C.N., Levin, D.E., Torres, E.R., Maxwell, A., Pollack, H.A., Moats, R.A., Frey, M.R., Darehzereshki, A., Al Alam, D., Lien, C.E., Grikscheit, T.C. (2015) Adult zebrafish intestine resection: a novel model of Short Bowel Syndrome, adaptation, and intestinal stem cell regeneration. American journal of physiology. Gastrointestinal and liver physiology. 309(3):G135-45.
Abstract
Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After two weeks, S1 was dilated compared to controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish, increased and contained a higher number of BrdU-labeled cells after 2 weeks of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish; a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping