BTBR ob/ob mice as a novel diabetic neuropathy model: Neurological characterization and gene expression analyses

Phillipe D. O'Brien, Junguk Hur, John M. Hayes, Carey Backus, Stacey A. Sakowski, Eva L. Feldman

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Given the lack of treatments for diabetic neuropathy (DN), a common diabetic complication, accurate disease models are necessary. Characterization of the leptin-deficient BTBR ob/. ob mouse, a type 2 diabetes model, demonstrated that the mice develop robust diabetes coincident with severe neuropathic features, including nerve conduction deficits and intraepidermal nerve fiber loss by 9 and 13. weeks of age, respectively, supporting its use as a DN model. To gain insight into DN mechanisms, we performed microarray analysis on sciatic nerve from BTBR ob/. ob mice, identifying 1503 and 642 differentially expressed genes associated with diabetes at 5 and 13. weeks, respectively. Further analyses identified overrepresentation of inflammation and immune-related functions in BTBR ob/. ob mice, which interestingly were more highly represented at 5. weeks, an observation that may suggest a contributory role in DN onset. To complement the gene expression analysis, we demonstrated that protein levels of select cytokines were significantly upregulated at 13. weeks in BTBR ob/. ob mouse sciatic nerve. Furthermore, we compared our array data to that from an established DN model, the C57BKS db/. db mouse, which reflected a common dysregulation of inflammatory and immune-related pathways. Together, our data demonstrate that BTBR ob/. ob mice develop rapid and robust DN associated with dysregulated inflammation and immune-related processes.

Original languageEnglish (US)
Pages (from-to)348-355
Number of pages8
JournalNeurobiology of Disease
Volume73
DOIs
StatePublished - Jan 1 2015

Keywords

  • Cytokine
  • Diabetic neuropathy
  • Functional enrichment
  • Gene expression analysis
  • Inflammation
  • Leptin
  • Matrix metalloproteinase
  • Mouse model
  • Obesity
  • Type-2 diabetes

ASJC Scopus subject areas

  • Neurology

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