Gene expression in intestinal mucosal biopsy specimens obtained from dogs with chronic enteropathy

Vicki L. Wilke Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.

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Dan Nettleton Department of Statistics, College of Liberal Arts and Sciences and the College of Agriculture and Life Sciences, Iowa State University, Ames, IA 50011.

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Meghan J. Wymore Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Jack M. Gallup Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Cumhur Yusuf Demirkale Department of Statistics, Institute of Food and Agricultural Sciences, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL 32611.

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Mark R. Ackermann Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Chris K. Tuggle Center for Integrated Genomics and Department of Animal Science, College of Agriculture and Life Sciences, Iowa State University, Ames, IA 50011.

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Amanda E. Ramer-Tait Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Michael J. Wannemuehler Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Albert E. Jergens Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Abstract

Objective—To characterize mucosal gene expression in dogs with chronic enteropathy (CE).

Animals—18 dogs with CE and 6 healthy control dogs.

Procedures—Small intestinal mucosal biopsy specimens were endoscopically obtained from dogs. Disease severity in dogs with CE was determined via inflammatory bowel index scores and histologic grading of biopsy specimens. Total RNA was extracted from biopsy specimens and microchip array analysis (approx 43,000 probe sets) and quantitative reverse transcriptase PCR assays were performed.

Results—1,875 genes were differentially expressed between dogs with CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with CE, including neurotensin, fatty acid–binding protein 6, fatty acid synthase, aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8, whereas few genes were upregulated in dogs with CE, including genes encoding products involved in extracellular matrix degradation (matrix metallopeptidases 1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome proliferator–activated receptor γ, and S100 calcium-binding protein G), iron transport (solute carrier family 40 member 1), and immunity (CD96 and carcinoembryonic antigen–related cell adhesion molecule [CEACAM] 18). Dogs with CE and protein-losing enteropathy had the greatest number of differentially expressed genes. Results of quantitative reverse transcriptase PCR assay for select genes were similar to those for microchip array analysis.

Conclusions and Clinical Relevance—Expression of genes encoding products regulating mucosal inflammation was altered in dogs with CE and varied with disease severity.

Impact for Human Medicine—Molecular pathogenesis of CE in dogs may be similar to that in humans with inflammatory bowel disease.

Abstract

Objective—To characterize mucosal gene expression in dogs with chronic enteropathy (CE).

Animals—18 dogs with CE and 6 healthy control dogs.

Procedures—Small intestinal mucosal biopsy specimens were endoscopically obtained from dogs. Disease severity in dogs with CE was determined via inflammatory bowel index scores and histologic grading of biopsy specimens. Total RNA was extracted from biopsy specimens and microchip array analysis (approx 43,000 probe sets) and quantitative reverse transcriptase PCR assays were performed.

Results—1,875 genes were differentially expressed between dogs with CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with CE, including neurotensin, fatty acid–binding protein 6, fatty acid synthase, aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8, whereas few genes were upregulated in dogs with CE, including genes encoding products involved in extracellular matrix degradation (matrix metallopeptidases 1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome proliferator–activated receptor γ, and S100 calcium-binding protein G), iron transport (solute carrier family 40 member 1), and immunity (CD96 and carcinoembryonic antigen–related cell adhesion molecule [CEACAM] 18). Dogs with CE and protein-losing enteropathy had the greatest number of differentially expressed genes. Results of quantitative reverse transcriptase PCR assay for select genes were similar to those for microchip array analysis.

Conclusions and Clinical Relevance—Expression of genes encoding products regulating mucosal inflammation was altered in dogs with CE and varied with disease severity.

Impact for Human Medicine—Molecular pathogenesis of CE in dogs may be similar to that in humans with inflammatory bowel disease.

Contributor Notes

Supported by an Oak grant from the American Kennel Club Canine Health Foundation.

Presented as an oral presentation at the 2009 European College of Veterinary Internal Medicine Congress, Porto, Portugal, September 2009.

Address correspondence to Dr. Jergens (ajergens@iastate.edu).
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