Lessons learned: optimization of a murine small bowel resection model.
OBJECTIVE
Central to the use of murine models of disease is the ability to derive reproducible data. The purpose of this study was to determine factors contributing to variability in our murine model of small bowel resection (SBR).


METHODS
Male C57Bl/6 mice were randomized to sham or 50% SBR. The effect of housing type (pathogen-free vs standard housing), nutrition (reconstituted powder vs tube feeding formulation), and correlates of intestinal morphology with gene expression changes were investigated. Multiple linear regression modeling or 1-way analysis of variance was used for data analysis.


RESULTS
Pathogen-free mice had significantly shorter ileal villi at baseline and demonstrated greater villus growth after SBR compared to mice housed in standard rooms. Food type did not affect adaptation. Gene expression changes were more consistent and significant in isolated crypt cells that demonstrated adaptive growth when compared with crypts that did not deepen after SBR.


CONCLUSIONS
Maintenance of mice in pathogen-free conditions and restricting gene expression analysis to individual animals exhibiting morphologic adaptation enhances sensitivity and specificity of data derived from this model. These refinements will minimize experimental variability and lead to improved understanding of the complex process of intestinal adaptation.
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Janice A
JA
Taylor
Colin A
CA
Martin
Rajalakshmi
R
Nair
Jun
J
Guo
Christopher R
CR
Erwin
Brad W
BW
Warner
D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020895:Enterocytes / Q000166:cytology* / Q000502:physiology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000601:surgery*; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D012778:Short Bowel Syndrome / Q000473:pathology* / Q000503:physiopathology