Analysis of gene expression in brain tissue from Greyhounds with meningoencephalitis

Kimberly A. Greer School of Natural Sciences and Mathematics, Indiana University East, Richmond, IN 47374.

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Paul Daly Section of Veterinary Pathobiology & Infectious Disease, School of Agriculture, Food Science & Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

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Keith E. Murphy Department of Genetics and Biochemistry, College of Engineerng and Science, Clemson University, Clemson, SC 29364.

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John J. Callanan Section of Veterinary Pathobiology & Infectious Disease, School of Agriculture, Food Science & Veterinary Medicine; and Conway Institute of Molecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

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Abstract

Objective—To elucidate the pathogenesis of Greyhound meningoencephalitis by evaluating gene expression in diseased brain tissue.

Animals—Cadavers of 3 diseased (8- to 15-month-old) and 3 (10-month-old) control Greyhounds.

Procedures—Samples of RNA were extracted from brain tissue of all dogs and evaluated by use of a canine-specific microarray.

Results—A unique profile involving significant alterations in expression of 21 genes was evident in diseased dogs, compared with expression in control dogs. Most genes with up-regulated expression were related to immune function, with the remaining genes involved in ligand binding, signal transduction, transcriptional regulation, and formation and transportation of proteins including enzymes. Of notable involvement were genes encoding for major histocompatibility complexes, small inducible cytokine A5 precursor, myxovirus-resistant proteins, and components of the classical complement pathway, which are all genes common to pathways of viral infections and autoimmunity.

Conclusions and Clinical Relevance—Although results of microarray analysis did not clearly define a potential etiology of Greyhound meningoencephalitis, they did highlight a consistent gene alteration signature that would suggest a common etiology and pathogenesis for this condition.

Abstract

Objective—To elucidate the pathogenesis of Greyhound meningoencephalitis by evaluating gene expression in diseased brain tissue.

Animals—Cadavers of 3 diseased (8- to 15-month-old) and 3 (10-month-old) control Greyhounds.

Procedures—Samples of RNA were extracted from brain tissue of all dogs and evaluated by use of a canine-specific microarray.

Results—A unique profile involving significant alterations in expression of 21 genes was evident in diseased dogs, compared with expression in control dogs. Most genes with up-regulated expression were related to immune function, with the remaining genes involved in ligand binding, signal transduction, transcriptional regulation, and formation and transportation of proteins including enzymes. Of notable involvement were genes encoding for major histocompatibility complexes, small inducible cytokine A5 precursor, myxovirus-resistant proteins, and components of the classical complement pathway, which are all genes common to pathways of viral infections and autoimmunity.

Conclusions and Clinical Relevance—Although results of microarray analysis did not clearly define a potential etiology of Greyhound meningoencephalitis, they did highlight a consistent gene alteration signature that would suggest a common etiology and pathogenesis for this condition.

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