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

Neurobiology of Disease

Stacey A. Sakowski¹  Junguk Hur²  Phillipe D. O'Brien²  Eva L. Feldman²  John M. Hayes²  Carey Backus² 

[1] A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI 48109, USA;Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA;

关键词: Type-2 diabetes;    Obesity;    Diabetic neuropathy;    Mouse model;    Leptin;    Gene expression analysis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown