O'Brien Phillipe D, Hur Junguk, Robell Nicholas J, Hayes John M, Sakowski Stacey A, Feldman Eva L
Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Basic Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
J Diabetes Complications. 2016 Jan-Feb;30(1):30-7. doi: 10.1016/j.jdiacomp.2015.09.018. Epub 2015 Oct 3.
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.
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.
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.
Similar to males, female BTBR ob/ob mice display robust DPN, and pathways related to inflammation are dysregulated in peripheral nerve.
为了鉴定糖尿病周围神经病变（DPN）的雌性小鼠模型，我们对雌性BTBR ob/ob小鼠的DPN进行了特征描述，并将它们的表型与非糖尿病且性别匹配的对照小鼠进行比较。我们还鉴定了雌性BTBR ob/ob小鼠坐骨神经（SCN）和背根神经节（DRG）中失调的基因和信号通路，以确定潜在的DPN机制。
终末神经病变表型分析包括检测对热刺激的潜伏期、坐骨神经运动和腓肠感觉神经传导速度（NCV）以及表皮内神经纤维（IENF）密度。对于基因表达谱分析，解剖DRG和SCN，分离RNA并使用微阵列技术进行处理，然后鉴定差异表达基因。
在研究结束时，雄性和雌性BTBR ob/ob小鼠均观察到类似的运动和感觉NCV缺陷；然而，雌性ob/ob小鼠的IENF密度高于雄性。与非糖尿病对照相比，雄性和雌性ob/ob小鼠均表现出相似的体重增加、高血糖和高胰岛素血症，尽管雄性甘油三酯升高幅度大于雌性。对雌性小鼠神经组织进行转录谱分析发现与炎症相关的信号通路失调。
与雄性相似，雌性BTBR ob/ob小鼠表现出明显的DPN，并且外周神经中与炎症相关的信号通路失调。
