| Authors |
O'Brien PD, Hur J, Hayes JM, Backus C, Sakowski SA, Feldman EL
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| Submitted By |
Eva Feldman on 12/8/2014 |
| Status |
Published |
| Journal |
Neurobiology of disease |
| Year |
2014 |
| Date Published |
10/30/2014 |
| Volume : Pages |
73C : 348 - 355 |
| PubMed Reference |
25447227 |
| 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
13weeks 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 13weeks, respectively. Further analyses identified
overrepresentation of inflammation and immune-related functions in BTBR ob/ob
mice, which interestingly were more highly represented at 5weeks, 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 13weeks 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.
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