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FS001: Aberrant gene expression in dogs with portosystemic shunts


ABSTRACT: Background: Congenital portosystemic shunts are developmental anomalies of the vascular system that cause portal blood to bypass the liver. Large-breed dogs are reported to have a predisposition for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs a predisposition for extrahepatic portosystemic shunts (EHPSS). While the physiological consequences of the two types of shunt are identical, the metabolic pathways involved are probably different. The aim of this study was to gain insight into the metabolic pathways involved in the different types of portosystemic shunting. Results: Microarray analysis of mRNA expression in liver tissue from dogs with EHPSS and IHPSS revealed that the expression of 26 genes was altered in either IHPSS or EHPSS samples compared with that in liver samples from control dogs. Quantitative real-time PCR of these genes in 14 IHPSS, 17 EHPSS, and 8 control liver samples revealed a significantly different expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry studies revealed that the pattern of VCAM1 and WEE1 protein expression supports the involvement of these proteins in the development of EHPSS and IHPSS, respectively. Conclusions: We identified a small list of genes possibly involved in two genetically different types of portosystemic shunt with identical pathophysiological consequences. WEE1 was found to be aberrantly expressed at an RNA and protein level in dogs with IHPSS. A decreased VCAM1 expression may play a role in the development of intrahepatic portal vascularization in dogs with EHPSS. Total RNA was isolated from liver tissue from 2 healthy dogs, 32 dogs with EHPSS, and 14 dogs with IHPSS. Pooled RNA isolated from healthy liver tissue was used as reference. Dye swap of Cy3 and Cy5 was performed to reduce dye bias.

ORGANISM(S): Canis lupus familiaris

SUBMITTER: Marian Groot Koerkamp 

PROVIDER: E-GEOD-39005 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Congenital portosystemic shunts are developmental anomalies of the splanchnic vascular system that cause portal blood to bypass the liver. Large-breed dogs are predisposed for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs for extrahepatic portosystemic shunts (EHPSS). While the phenotype resulting from portal bypass of the liver of the two types of shunt is identical, the genotype and molecular pathways involved are probably different. The aim of this study was to gain insight i  ...[more]

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