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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.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE39005 | GEO | 2013/03/01

SECONDARY ACCESSION(S): PRJNA169652

REPOSITORIES: GEO

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FS001: Aberrant gene expression in dogs with portosystemic shunts

Project description: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.

2013-03-01 | E-GEOD-39005 | biostudies-arrayexpress

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Expression data from patients of idiopathic portal hypertension

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Comparison against 186 canid whole genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor

Project description:Whole genome sequencing of CTVT, breed dogs, and wild canids reveals pathways that are important in cancer cell survival. Comparison of these mutations with breed dogs shows that the original tumor came from a dog very similar to one of the modern Arctic breeds. DNA was collected from pedigreed dogs of the Alaskan Malamute (AMAL) and Siberian Husky (HUSK) breeds living in North America. SNPs were genotyed using the Illumina CanineHD SNP chip. These SNPs were compared to published data and seqeunced mutations from CTVT by principal component alnalysis to identify the breed of the CTVT originator.

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RNA-Seq of anterior cruciate ligament and knee joint synovium in dogs that are affected with cruciate rupture compared to matched controls.

Project description:The intent of the experiment was to identify genes that were differentially expressed between dogs affected with anterior cruciate ligament (ACL) rupture and breed-matched controls. Anterior cruciate ligament and knee synovial tissue biopsies were collected from 4 ACL rupture affected cases and 4 unaffected control dogs. Cases and controls were matched as closely as possible based on breed, sex, neutered status, age, and weight. Medications that the dogs were taking at the time of sample collection were also considered. We prioritized sample size and quality above all other variables, therefore, two matched pairs of Golden Retrievers were chosen with two matched pairs of Labrador Retrievers for this analysis. Tissues from cases were collected during knee stabilization surgery. Tissues from unaffected control dogs were collected from dogs undergoing pelvic limb amputation or euthanasia for reasons unrelated to this study. Illumina TruSeq RNA libraries were constructed and 150bp paired-end sequencing was performed using the Illumina Hi-Seq 2500 platform. Table 1. Breed, sex, age, and weight of matched case and control pairs chosen for RNA sequencing analysis Cases Matched Controls Breed Sex Age (yr) Weight (kg) Breed Sex Age (yr) Weight (kg) GR1 CM 8.8 30.5 GR2 CM 14.9 N/A GR3 CM 5.6 44.0 GR4 CM 3.9 34.0 LR1 CM 9.7 36.0 LR2 CM 12.7 28.5 LR3 CM 13.3 36.0 LR4 CM 13.5 35.0 GR = Golden Retriever. LR = Labrador Retriever. CM= castrated male. Weight at the time of death was not available for one dog.

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Is Increased Sinusoidal Flow in the Liver Remnant the primary Stimulus to Regeneration after partial Hepatectomy

Project description:The impact of portal arterialization on the liver parenchyma was studied in a series of six pigs with aortoportal shunting of liver segments II, III and IV (and 6 sham animals). Gene expression in the arterialized segments was compared to expression in sham animals. Primary endpoints were gene expression profiles in the hyperperfused segments at sampling time points 1, 5, 10, 30, 60, 90 minutes and 2, 3, 4 and 6 hours after shunt opening. Keywords: time course, treatment comparison Six pigs were treated with aortoportal shunting of segments II, III and IV and six animals were subject to sham surgery. Expression profiling was conducted by hybridizing each sample against a common reference, consisting of liver RNA from an unrelated animal..

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