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

Details

• Personal Author:
  Ashbrook DG ; Jones BC ; Lu L ; Miller DB ; Mulligan MK ; O'Callaghan JP ; Torres-Rojas C ; Williams RW ; Xu F ; Zhao W ; Zhuang D
• 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. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Genetics Immune System Laboratories Nervous System Nervous System Diseases Occupational Health Pathology Phosphoric Acids Safety Sex Characteristics

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• Keywords:
  Animal Studies Author Keywords: BXD Mice Brain Function Brain Matter Candidate Gene Corticosteroids Corticosterone DFP Gene Expression Genes Genetic Predisposition Immune Reaction Laboratory Animals Laboratory Testing Neuroinflammation Neurological Disorders Organophosphorus Compounds Phosphates Recombinant Inbred Strains Ribonucleic Acids RNA Sex Factors Synergism

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• ISSN:
  2076-3425
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; OSHA Region 4 ; Tennessee ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  10
• Issue:
  3
• NIOSHTIC Number:
  nn:20059114
• Citation:
  Brain Sci 2020 Mar; 10(3):143
• Contact Point Address:
  Byron C. Jones, Department of Genetics, Genomics and Informatics, Department of Pharmacology, University of Tennessee Health Science Center, 71 South Manassas Street, Memphis, TN 38163, USA
• Email:
  bjone129@uthsc.edu
• CAS Registry Number:
  Diisopropyl fluorophosphate (CAS RN 55-91-4)
• Federal Fiscal Year:
  2020
• Peer Reviewed:
  True
• Source Full Name:
  Brain Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:83b1b6cc320b15b25321dcf458b5a1f52b83f6fc32b0c0e8981418fa0fb1663e4ea43e19aaf9b71ac19960e7a776b44dfdd98ff822635ffb20c0be2b63d361c2
• Download URL:
  https://stacks.cdc.gov/view/cdc/223428/cdc_223428_DS1.pdf
• File Type:
  [PDF - 4.40 MB ]