title: An exploration of heat tolerance in mice utilizing mRNA and microRNA expression analysis.
abstract: BACKGROUND
  Individuals who rapidly develop hyperthermia during heat exposure (heat-intolerant) are vulnerable to heat associated illness and injury. We recently reported that heat intolerant mice exhibit complex alterations in stress proteins in response to heat exposure. In the present study, we further explored the role of genes and molecular networks associated with heat tolerance in mice.
  
  
  METHODS
  Heat-induced physiological and biochemical changes were assessed to determine heat tolerance levels in mice. We performed RNA and microRNA expression profiling on mouse gastrocnemius muscle tissue samples to determine novel biological pathways associated with heat tolerance.
  
  
  RESULTS
  Mice (n = 18) were assigned to heat-tolerant (TOL) and heat-intolerant (INT) groups based on peak core temperatures during heat exposures. This was followed by biochemical assessments (Hsp40, Hsp72, Hsp90 and Hsf1 protein levels). Microarray analysis identified a total of 3,081 mRNA transcripts that were significantly misregulated in INT compared to TOL mice (p<0.05). Among them, Hspa1a, Dnajb1 and Hspb7 were differentially expressed by more than two-fold under these conditions. Furthermore, we identified 61 distinct microRNA (miRNA) sequences significantly associated with TOL compared to INT mice; eight miRNAs corresponded to target sites in seven genes identified as being associated with heat tolerance pathways (Hspa1a, Dnajb1, Dnajb4, Dnajb6, Hspa2, Hspb3 and Hspb7).
  
  
  CONCLUSIONS
  The combination of mRNA and miRNA data from the skeletal muscle of adult mice following heat stress provides new insights into the pathophysiology of thermoregulatory disturbances of heat intolerance.
authors: Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America. aminul.islam@usuhs.edu
authors: Aminul
authors: A
authors: Islam
authors: Patricia A
authors: PA
authors: Deuster
authors: Joseph M
authors: JM
authors: Devaney
authors: Svetlana
authors: S
authors: Ghimbovschi
authors: Yifan
authors: Y
authors: Chen
mesh_terms: D000818:Animals; D015415:Biomarkers; D016000:Cluster Analysis; D005334:Fever / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D018869:Heat-Shock Response / Q000235:genetics*; D006358:Hot Temperature; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger
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