Expression of selected genes isolated from whole blood, liver and obex in lambs with experimental classical scrapie and healthy controls, showing a systemic innate immune response at the clinical end-stage

TY - JOUR

T1 - Expression of selected genes isolated from whole blood, liver and obex in lambs with experimental classical scrapie and healthy controls, showing a systemic innate immune response at the clinical end-stage

AU - Meling, Siv

AU - Skovgaard, Kerstin

AU - Bårdsen, Kjetil

AU - Heegaard, Peter Mikael Helweg

AU - Ulvund, Martha J.

N1 - This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

PY - 2018

Y1 - 2018

N2 - Background: Incubation period, disease progression, pathology and clinical presentation of classical scrapie in sheep are highly dependent on PRNP genotype, time and route of inoculation and prion strain. Our experimental model with pre-colostrum inoculation of homozygous VRQ lambs has shown to be an effective model with extensive PrPSc dissemination in lymphatic tissue and a short incubation period with severe clinical disease. Serum protein analysis has shown an elevation of acute phase proteins in the clinical stages of this experimental model, and here, we investigate changes in gene expression in whole blood, liver and brain. Results: The animals in the scrapie group showed severe signs of illness 22 weeks post inoculation necessitating euthanasia at 23 weeks post inoculation. This severe clinical presentation was accompanied by changes in expression of several genes. The following genes were differentially expressed in whole blood: TLR2, TLR4, C3, IL1B, LF and SAA, in liver tissue, the following genes differentially expressed: TNF-α, SAA, HP, CP, AAT, TTR and TF, and in the brain tissue, the following genes were differentially expressed: HP, CP, ALB and TTR. Conclusions: We report a strong and evident transcriptional innate immune response in the terminal stage of classical scrapie in these animals. The PRNP genotype and time of inoculation are believed to contribute to the clinical presentation, including the extensive dissemination of PrPSc throughout the lymphatic tissue. 

AB - Background: Incubation period, disease progression, pathology and clinical presentation of classical scrapie in sheep are highly dependent on PRNP genotype, time and route of inoculation and prion strain. Our experimental model with pre-colostrum inoculation of homozygous VRQ lambs has shown to be an effective model with extensive PrPSc dissemination in lymphatic tissue and a short incubation period with severe clinical disease. Serum protein analysis has shown an elevation of acute phase proteins in the clinical stages of this experimental model, and here, we investigate changes in gene expression in whole blood, liver and brain. Results: The animals in the scrapie group showed severe signs of illness 22 weeks post inoculation necessitating euthanasia at 23 weeks post inoculation. This severe clinical presentation was accompanied by changes in expression of several genes. The following genes were differentially expressed in whole blood: TLR2, TLR4, C3, IL1B, LF and SAA, in liver tissue, the following genes differentially expressed: TNF-α, SAA, HP, CP, AAT, TTR and TF, and in the brain tissue, the following genes were differentially expressed: HP, CP, ALB and TTR. Conclusions: We report a strong and evident transcriptional innate immune response in the terminal stage of classical scrapie in these animals. The PRNP genotype and time of inoculation are believed to contribute to the clinical presentation, including the extensive dissemination of PrPSc throughout the lymphatic tissue. 

KW - Classical scrapie

KW - Innate immune response

KW - qPCR

KW - Whole blood

KW - Liver tissue

KW - Brain tissue

KW - Sheep

U2 - 10.1186/s12917-018-1607-9

DO - 10.1186/s12917-018-1607-9

M3 - Journal article

VL - 14

JO - B M C Veterinary Research

JF - B M C Veterinary Research

SN - 1746-6148

M1 - 281

ER -