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Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness

Between 25% and 30% of the nearly one million military personnel who participated in the 1991 Persian Gulf War became ill with chronic symptoms ranging from gastrointestinal to nervous system dysfunction. This disorder is now referred to as Gulf War Illness (GWI) and the underlying pathophysiology h...

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Autores principales: Jones, Byron C., Miller, Diane B., Lu, Lu, Zhao, Wenyuan, Ashbrook, David G., Xu, Fuyi, Mulligan, Megan K., Williams, Robert W., Zhuang, Daming, Torres-Rojas, Carolina, O’Callaghan, James P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139661/
https://www.ncbi.nlm.nih.gov/pubmed/32131477
http://dx.doi.org/10.3390/brainsci10030143
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author Jones, Byron C.
Miller, Diane B.
Lu, Lu
Zhao, Wenyuan
Ashbrook, David G.
Xu, Fuyi
Mulligan, Megan K.
Williams, Robert W.
Zhuang, Daming
Torres-Rojas, Carolina
O’Callaghan, James P.
author_facet Jones, Byron C.
Miller, Diane B.
Lu, Lu
Zhao, Wenyuan
Ashbrook, David G.
Xu, Fuyi
Mulligan, Megan K.
Williams, Robert W.
Zhuang, Daming
Torres-Rojas, Carolina
O’Callaghan, James P.
author_sort Jones, Byron C.
collection PubMed
description Between 25% and 30% of the nearly one million military personnel who participated in the 1991 Persian Gulf War became ill with chronic symptoms ranging from gastrointestinal to nervous system dysfunction. This disorder is now referred to as Gulf War Illness (GWI) and the underlying pathophysiology has been linked to exposure-based neuroinflammation caused by organophosphorous (OP) compounds coupled with high circulating glucocorticoids. In a mouse model of GWI we developed, corticosterone was shown to act synergistically with an OP (diisopropylflurophosphate) to dramatically increase proinflammatory cytokine gene expression in the brain. Because not all Gulf War participants became sick, the question arises as to whether differential genetic constitution might underlie individual differences in susceptibility. To address this question of genetic liability, we tested the impact of OP and glucocorticoid exposure in a genetic reference population of 30 inbred mouse strains. We also studied both sexes. The results showed wide differences among strains and overall that females were less sensitive to the combined treatment than males. Furthermore, we identified one OP-glucocorticoid locus and nominated a candidate gene—Spon1—that may underlie the marked differences in response.
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spelling pubmed-71396612020-04-10 Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness Jones, Byron C. Miller, Diane B. Lu, Lu Zhao, Wenyuan Ashbrook, David G. Xu, Fuyi Mulligan, Megan K. Williams, Robert W. Zhuang, Daming Torres-Rojas, Carolina O’Callaghan, James P. Brain Sci Article Between 25% and 30% of the nearly one million military personnel who participated in the 1991 Persian Gulf War became ill with chronic symptoms ranging from gastrointestinal to nervous system dysfunction. This disorder is now referred to as Gulf War Illness (GWI) and the underlying pathophysiology has been linked to exposure-based neuroinflammation caused by organophosphorous (OP) compounds coupled with high circulating glucocorticoids. In a mouse model of GWI we developed, corticosterone was shown to act synergistically with an OP (diisopropylflurophosphate) to dramatically increase proinflammatory cytokine gene expression in the brain. Because not all Gulf War participants became sick, the question arises as to whether differential genetic constitution might underlie individual differences in susceptibility. To address this question of genetic liability, we tested the impact of OP and glucocorticoid exposure in a genetic reference population of 30 inbred mouse strains. We also studied both sexes. The results showed wide differences among strains and overall that females were less sensitive to the combined treatment than males. Furthermore, we identified one OP-glucocorticoid locus and nominated a candidate gene—Spon1—that may underlie the marked differences in response. MDPI 2020-03-02 /pmc/articles/PMC7139661/ /pubmed/32131477 http://dx.doi.org/10.3390/brainsci10030143 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jones, Byron C.
Miller, Diane B.
Lu, Lu
Zhao, Wenyuan
Ashbrook, David G.
Xu, Fuyi
Mulligan, Megan K.
Williams, Robert W.
Zhuang, Daming
Torres-Rojas, Carolina
O’Callaghan, James P.
Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
title Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
title_full Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
title_fullStr Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
title_full_unstemmed Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
title_short Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
title_sort modeling the genetic basis of individual differences in susceptibility to gulf war illness
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139661/
https://www.ncbi.nlm.nih.gov/pubmed/32131477
http://dx.doi.org/10.3390/brainsci10030143
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