title: Gender-specific differences in diabetic neuropathy in BTBR ob/ob mice.
abstract: OBJECTIVE
  To identify a female mouse model of diabetic peripheral neuropathy (DPN), we characterized DPN in female BTBR ob/ob mice and compared their phenotype to non-diabetic and gender-matched controls. We also identified dysregulated genes and pathways in sciatic nerve (SCN) and dorsal root ganglia (DRG) of female BTBR ob/ob mice to determine potential DPN mechanisms.
  
  
  METHODS
  Terminal neuropathy phenotyping consisted of examining latency to heat stimuli, sciatic motor and sural sensory nerve conduction velocities (NCV), and intraepidermal nerve fiber (IENF) density. For gene expression profiling, DRG and SCN were dissected, RNA was isolated and processed using microarray technology and differentially expressed genes were identified.
  
  
  RESULTS
  Similar motor and sensory NCV deficits were observed in male and female BTBR ob/ob mice at study termination; however, IENF density was greater in female ob/ob mice than their male counterparts. Male and female ob/ob mice exhibited similar weight gain, hyperglycemia, and hyperinsulinemia compared to non-diabetic controls, although triglycerides were elevated more so in males than in females. Transcriptional profiling of nerve tissue from female mice identified dysregulation of pathways related to inflammation.
  
  
  CONCLUSIONS
  Similar to males, female BTBR ob/ob mice display robust DPN, and pathways related to inflammation are dysregulated in peripheral nerve.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Phillipe D
authors.initials: PD
authors.lastname: O'Brien
authors.affiliation: Department of Basic Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Junguk
authors.initials: J
authors.lastname: Hur
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Robell
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Hayes
authors.affiliation: A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Sakowski
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: efeldman@med.umich.edu.
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004817:Epidermis / Q000294:innervation; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006358:Hot Temperature / Q000009:adverse effects; D015228:Hypertriglyceridemia / Q000150:complications; D008297:Male; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009048:Motor Skills; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009431:Neural Conduction; D009765:Obesity / Q000150:complications*; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time; D012584:Sciatic Nerve / Q000378:metabolism* / Q000503:physiopathology; D055139:Sensory Gating; D012727:Sex Characteristics
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger
keywords: Animal models; Diabetic peripheral neuropathy; Dyslipidemia; Gene expression; Type 2 diabetes