| First Author | O'Brien PD | Year | 2015 |
| Journal | Neurobiol Dis | Volume | 73 |
| Pages | 348-55 | PubMed ID | 25447227 |
| Mgi Jnum | J:260940 | Mgi Id | MGI:6141551 |
| Doi | 10.1016/j.nbd.2014.10.015 | Citation | O'Brien PD, et al. (2015) BTBR ob/ob mice as a novel diabetic neuropathy model: Neurological characterization and gene expression analyses. Neurobiol Dis 73:348-55 |
| abstractText | 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. |
