【作者】 刘三妹；

【导师】 资晓宏；

【作者基本信息】 中南大学 ， 神经病学， 2011， 硕士

【摘要】 腓骨肌萎缩症(Charcot-Marie-Tooth disease, CMT)具有高度的临床和遗传异质性,是最常见遗传性的周围神经病,临床上以肢体远端肌肉的进行性对称性的无力、萎缩、感觉减退和腱反射减弱等为主要特征,发病率约为1/2500。根据病理学和电生理特点,临床上依据其病理和电生理特点可分为两型：脱髓鞘型(CMT1型)和轴突型(CMT2型),根据遗传方式不同,腓骨肌萎缩症可分为常染色体隐性遗传(AR)、常染色体显性遗传(AD)、和X连锁遗传(XD/XR)。研究表明,腓骨肌萎缩症各亚型致病基因的具体分子发病机制并不完全相同,可能是通过致病基因的功能丧失、功能获得、剂量效应、显性-负性作用而致病。本实验采取基因鉴定和行为学分析方法验证该携带人类突变的pCAGGS-HA-K141NHSPB8转基因小鼠。基因鉴定结果表明F3代有9只pCAGGS-HA-K141NHSPB8转基因小鼠和9只pCAGGS-HA-wtHSPB8转基因小鼠。行为学方法包括足迹实验、固定棒试验、旋转棒试验、痛阈实验。足迹实验方差分析结果：MT(突变组)、WT(过表达组)、NT(正常组)三组F2,F3代足迹分析足印长、步长随机区组设计资料方差分析多重比较p<0.05,有统计学意义；固定棒试验结果MT、WT小鼠运动协调能力较NT小鼠较运动协调能力降低；MT F3代在转棒上停留时间明显少于NT和WT的F3代在转棒上停留时间,p<0.05。旋转棒试验结果表明pCAGGS-HA-K141NHSPB8突变小鼠下肢周围神经运动功能受损；足底电击痛阈实验统计学方差分析,p>0.05, MT, WT, NT三种基因型的小鼠之间的痛阈值无明显差异,表明pCAGGS-HA-K141NHSPB8突变小鼠下肢周围感觉神经无明显受累。更多还原

【Abstract】 Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN), is the most common hereditary peripheral neuropathy with highly clinical and genetic heterogeneity. CMT is characterized by progressive and symmetric distal muscle atrophy, weakness, hyporeflexia and hypoesthesia in distal limbs. The incidence of CMT is about 1/2500. According to the electrophysiological and histopathological criteria, CMT can be divided into two forms:the demyelinating form (CMT1) and the axonal form (CMT2). Several modes of inheritance have been described in CMT, including autosomal dominant (AD), autosomal recessive (AR) and X-linked dominant or recessive (XD/XR).Although many mutations of a number of genes have been associated with CMT, the disease mechanisms caused by each gene may be different. The main mechanisms include dosage effect, loss of function, gain of function or dominant-negative effect.This experiment wo breed the transgenic mice which carry mutation of human pCAGGS-HA-K141N HSPB8 gene by behavior analysis and gene identification.we gain nine pCAGGS-HA-K141N HSPB8 and nine pCAGGS -HA-WT HSPB8 gene transgenic mouse. The behavior tests contain footprinting test, bar test, rotarod test and foot sole lancinating pain threshold test. The result of footprinting test analysis of variance:the randomized block design material anova multiple comparison of the F2 and F3 transgenic mice mutations group(MT),over expressing group(WT)and normal group(NT):p<0.05, have statistical significance. The result of bar test analysis of variance:the motor coordination ability of transgenic mice mutations group and over expressing group are less than normal group; The time of F3 transgenic mice mutations group in fixed stick are less than over expressing group (WT) and normal group(NT):p<0.05, have statistical significance. The result of Rotating experiment:the lower extremity peripheral nerve of transgenic mice mutations group have damaged in movement function. The result of foot sole lancinating pain threshold experiment analysis of variance:p>0.05, have no statistical significance.更多还原