剔除小鼠神经微管运动蛋白Kif1b基因产生轴索型神经退行性病变  

Knockout neuronal microtubule motor protein Kif1b gene producing axonal neuron degeneration

作　　者：董铭[1] 于澎[2] 饶明俐[1] 田中庸介[3] 

机构地区：[1]吉林大学第一医院神经内科,吉林长春130021 [2]吉林大学第二医院眼科,吉林长春130041 [3]东京大学医学部

出　　处：《中风与神经疾病杂志》2008年第3期274-276,共3页Journal of Apoplexy and Nervous Diseases

摘　　要：目的研究杂合子小鼠Kif1b基因剔除后神经系统的病理改变,为Charcot-Marie-Tooth(CMT)病动物模型的分型提供病理学依据。方法用PCR和Southern blotting检测基因型和验证同源重组,通过脊髓前角细胞HE染色和坐骨神经甲苯胺蓝染色及电镜标本制备观察病理改变。结果Kif1b基因组DNA用Southern blotting检测表明,PCR法挑选的19只小鼠全部发生了同源重组。杂合子Kif1b基因剔除小鼠的坐骨神经内,粗径有髓纤维轴索变性,数量减少。在光镜和电镜下可见轴索的限局性肿胀,肿胀处可见壅堵的细胞器,但未见髓鞘的改变、节段性脱髓鞘和"洋葱球"样改变;其脊髓前角细胞体中,HE染色可以看到典型的嗜酸性球状体变性,电镜下显示为各种细胞器堵塞在核周和在细胞通往轴索的出口处,包括排列紊乱的神经丝、线粒体、空泡及多室小体。脊髓前角细胞数目明显减少。结论杂合子Kif1b基因剔除小鼠的病理改变与人类CMT2A具有相似性。Objective To investigate the pathology of heterozygous kiflb gene knockout mice as an animal model of Charcot-Marie-Tooth（CMT） disease. Methods Checking homologous recombination and genotype by southern blotting and PCR, surveying pathological changes in HE staining of spinal anterior horn,in CBB staining of sciatic nerve and in electron microscope. Results Southern blotting results showed homologous recombination happened in all of the 19 heterozygous kiflb knockout mice checked by PCR. Heterozygous Kiflb knockout mice showed axonal neuron degeneration and number decreasing in large diameter axons. Obstructed cellular organelles were found in local axon enlargement under light microscopy and electron microscopy ,no change was found in myelinated fibers, segmental demyelation and onion bulb formation were not found. Typical acidophily sphenoid bodies were found in anterior horn cell bodies. Various cellular organelles clogged around nuclear and in axon entering region, including mussy neurofilament, mitochondria, vacuole and multi-vescular body, Neuronal numbers of spinal anterior horn decreased significantly. Conclusion The heterozygous Kiflb knockout mice mimic the pathological changes of human CMT disease. It is feasible to use those mice as animal model of CMT disease.

关 键 词：微管运动蛋白 基因剔除 CHARCOT-MARIE-TOOTH病 病理学 

分 类 号：Q343[生物学—遗传学]