東北大学大学院農学研究科
食と農免疫国際教育研究センター

CFAI 特別セミナー
2023年10月30日

月 13:00-14:00

会場：第４講義室
Assessing genetic and epigenetic contributions to the ovine stress response phenotype
using bacterial endotoxin

Dr. Niel KarrowProfessor, University of Guelph
Adjunct professor, Tohoku University
When livestock are reared using intensive farming practices, they experience increased stressthat can adversely affect animal health and production, and climate change is predicted to be anamplifying factor. Producers have become reliant on antimicrobials to prevent and treat diseases causedby microbial stressors however, this global practise is facing increasing restrictions because it hascontributed to the development of antimicrobial resistant pathogens, some of which are zoonotic.
Selective breeding based on a health trait such as stress responsiveness may be a strategy to improve
population level stress resilience, and this would help to mitigate adverse outcomes attributed to stress.
Stress responsiveness is a moderately heritable trait, but estimates vary with phenotyping methods.
Bacterial lipopolysaccharide (LPS) endotoxin has been widely used across species as a microbial
stressor. When an LPS immune challenge is carried out on sheep, it elicits a classical acute-phase
response (APR) that manifests as fever, anorexia and temporal increases in serum cytokine and stresshormone (cortisol) levels that model an acute bacterial infection. Bacterial LPS is a biologically relevant
stressor implicated in numerous disorders including mastitis, sepsis, acidosis, and leaky gut syndrome, allof which are exacerbated by heat stress. Our group has been using LPS to stress phenotype sheep forseveral years. We have demonstrated that the peak cortisol response to LPS is correlated with immune
responsiveness, and telomere length, which is a predictive marker of ageing. This phenotype ismoderately heritable (h2≅0.3), and we have identified several genetic markers associated with stressresponsiveness using this phenotyping platform. Interestingly, LPS immune challenge during pregnancy
alters ovine fetal neuroendocrine-immune programming, and this is retained into adulthood. The
mechanisms by which this occurs are currently unknown, however, epigenetic mechanisms that include
microRNA (miRNA) have been implicated in fetal reprogramming. Recently, we identified 45 ovine
miRNAs (35 upregulated and 10 downregulated) that were differentially expressed (DE) during the peakstress response to LPS immune challenge, most of which are found on ovine chromosome 18. Further
analysis of high (HSR), middle (MSR) and low (LSR) stress responding sheep from a population of 112
animals revealed 3 upregulated and 7 downregulated DE miRNA (HSR versus MSR and LSR). Functional
analysis of these DE miRNAs revealed roles in Ras and MAPK signaling, cytokine signaling, adaptive
immune system and transcriptional pathways in the HSR sheep. In contrast, metabolic pathways wereenriched in the LSR sheep. Collectively, these studies reveal roles for miRNAs in the ovine stressresponse that should be investigated further to elucidate their contribution to regulating mRNA expression
during LPS-induced stress, and genetic and epigenetic variation in stress responsiveness.

乳房炎の予防・治療を目的とした研究はこれまで多数行われておりますが、乳房炎の発症そのものを予防可能な乳房炎ワクチンは未だ開発されておらず、そのための基礎研究の進展は急務とされています。
本セミナーでは、我々のグループがこれまで明らかにしてきた、乳腺免疫系の発達を促す分子メカニズムを紹介することで、乳房炎ワクチン開発に向けた今後の基礎研究の方向性を、皆さんと議論したいと思います。

問合わせ先：
野地智法（4312）
nochi@tohoku.ac.jp