Epigenetic Analysis in a Murine Genetic Model of Gulf War Illness

Details

• Personal Author:
  Ashbrook DG ; Jones BC ; Lu L ; Mozhui K ; O'Callaghan JP ; Prins P ; Zhao W
• Description:
  Of the nearly 1 million military personnel who participated in the 1990-1991 Gulf War, between 25% and 35% became ill with what now is referred to as Gulf War Illness (GWI) by the Department of Defense. Symptoms varied from gastrointestinal distress to lethargy, memory loss, inability to concentrate, depression, respiratory, and reproductive problems. The symptoms have persisted for 30 years in those afflicted but the basis of the illness remains largely unknown. Nerve agents and other chemical exposures in the war zone have been implicated but the long-term effects of these acute exposures have left few if any identifiable signatures. The major aim of this study is to elucidate the possible genomic basis for the persistence of symptoms, especially of the neurological and behavioral effects. To address this, we performed a whole genome epigenetic analysis of the proposed cause of GWI, viz., exposure to organophosphate neurotoxicants combined with high circulating glucocorticoids in two inbred mouse strains, C57BL/6J and DBA/2J. The animals received corticosterone in their drinking water for 7 days followed by injection of diisopropylfluorophosphate, a nerve agent surrogate. Six weeks after DFP injection, the animals were euthanized and medial prefrontal cortex harvested for genome-wide DNA methylation analysis using high-throughput sequencing. We observed 67 differentially methylated genes, notably among them, Ttll7, Akr1c14, Slc44a4, and Rusc2, all related to different symptoms of GWI. Our results support proof of principle of genetic differences in the chronic effects of GWI-related exposures and may reveal why the disease has persisted in many of the now aging Gulf War veterans. [Description provided by NIOSH]
• Subjects:
  Animals Behavior Epidemiology Genetics Hazardous Substances Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Animal Studies Author Keywords: MBD-seq Chemical Hazards Corticosterone Diisopropyl Fluorophosphate DNA Damage DNA Methylation Genes Genetic Factors Genetics Genomics Military Personnel Neurological Disorders Systems

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• ISSN:
  2673-3080
• 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:
  5
• NIOSHTIC Number:
  nn:20067911
• Citation:
  Front Toxicol 2023 Jun; 5:1162749
• Contact Point Address:
  Khyobeni Mozhui, Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
• Email:
  kmozhui@uthsc.edu
• Federal Fiscal Year:
  2023
• Peer Reviewed:
  True
• Source Full Name:
  Frontiers in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:59520cfd3e9c2485de2110c53562a23495ff63fae704fcee7327171078982b6ce1dcd5166ab7a8e31bac78efac5bedb9b73573a7f39e19386e98eed704d9b9dc
• Download URL:
  https://stacks.cdc.gov/view/cdc/230145/cdc_230145_DS1.pdf
• File Type:
  [PDF - 1.37 MB ]