title: Aberrant gene expression in dogs with portosystemic shunts.
abstract: 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 into the pathways involved in the different types of portosystemic shunting. 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 significant differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry and Western blotting confirmed an increased expression of VCAM1 in IHPSS but its absence in EHPSS, an increased WEE1 expression in IHPSS but not in EHPSS, and a decreased expression of CCBL1 in both shunt types. Regarding their physiologic functions, these findings may indicate a causative role for VCAM1 in EHPSS [corrected] and WEE1 for IHPSS. CCBL1 could be an interesting candidate to study not yet elucidated aspects in the pathophysiology of hepatic encephalopathy.
authors: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. f.g.vansteenbeek@uu.nl
authors: Frank G
authors: FG
authors: van Steenbeek
authors: Lindsay
authors: L
authors: Van den Bossche
authors: Guy C M
authors: GC
authors: Grinwis
authors: Anne
authors: A
authors: Kummeling
authors: Ingrid H M
authors: IH
authors: van Gils
authors: Marian J A Groot
authors: MJ
authors: Koerkamp
authors: Dik
authors: D
authors: van Leenen
authors: Frank C P
authors: FC
authors: Holstege
authors: Louis C
authors: LC
authors: Penning
authors: Jan
authors: J
authors: Rothuizen
authors: Peter A J
authors: PA
authors: Leegwater
authors: Bart
authors: B
authors: Spee
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000151:congenital / Q000235:genetics* / Q000601:surgery; D004285:Dogs; D015870:Gene Expression; D006501:Hepatic Encephalopathy / Q000235:genetics / Q000662:veterinary; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D010641:Phenotype; D011169:Portal Vein / Q000002:abnormalities / Q000378:metabolism* / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome; D054079:Vascular Malformations / Q000235:genetics / Q000601:surgery / Q000662:veterinary*
chemical_list: D012333:RNA, Messenger