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Published on: November 18, 2016
Aberrant gene expression in dogs with portosystemic shunts
Frank G van Steenbeek1, Lindsay Van den Bossche, Guy C M Grinwis
1Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. f.g.vansteenbeek@uu.nl
Plos One
|March 2, 2013
Summary
Congenital portosystemic shunts in dogs, affecting large and small breeds differently, involve distinct molecular pathways. This study identified specific gene expression changes, highlighting VCAM1 and WEE1 as potentially causative in intrahepatic and extrahepatic shunts, respectively.
Area of Science:
- Veterinary Medicine
- Molecular Biology
- Genetics
Background:
- Congenital portosystemic shunts (CPSS) are vascular anomalies where portal blood bypasses the liver.
- Intrahepatic portosystemic shunts (IHPSS) are common in large-breed dogs, while extrahepatic portosystemic shunts (EHPSS) occur in small breeds.
- Despite similar clinical signs, the underlying genetic and molecular mechanisms of IHPSS and EHPSS are likely different.
Purpose of the Study:
- To investigate the molecular pathways and gene expression differences between IHPSS and EHPSS in dogs.
- To identify specific genes associated with the distinct types of congenital portosystemic shunts.
Main Methods:
- Microarray analysis of liver mRNA expression in dogs with EHPSS, IHPSS, and control dogs.
- Quantitative real-time PCR to validate differential gene expression of selected genes.
- Immunohistochemistry and Western blotting to confirm protein expression levels of key genes.
Main Results:
- Microarray analysis revealed altered expression of 26 genes in IHPSS or EHPSS compared to controls.
- Quantitative PCR confirmed differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1.
- VCAM1 and WEE1 showed increased expression in IHPSS, while CCBL1 was decreased in both IHPSS and EHPSS.
Conclusions:
- VCAM1 may play a causative role in EHPSS, and WEE1 in IHPSS.
- CCBL1 warrants further investigation for its role in the pathophysiology of hepatic encephalopathy.
- These findings provide insights into the distinct molecular underpinnings of different congenital portosystemic shunt types in dogs.
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