周围神经单基因遗传病腓骨肌萎缩症的转基因小鼠模型

中国中南大学湘雅三医院张如旭博士所在团队既往研究发现,小热休克蛋白8的K141N突变与中国腓骨肌萎缩症2L型家系有关。为此,他们建立了一个人小热休克蛋白8基因K141N突变的转基因小鼠模型,用于周围神经单基因遗传病腓骨肌萎缩症的研究。结果发现转基因小鼠6个月时后肢肌肉力量及运动功能减弱,且坐骨神经轴突形态和功能都出现退化,而髓鞘未出现病变。

SICENCE新闻发布 作者：张如旭 稿号：nrr-15-13 周围神经单基因遗传病腓骨肌萎缩症的转基因小鼠模型

中国中南大学湘雅三医院张如旭博士所在团队既往研究发现，小热休克蛋白8的K141N突变与中国腓骨肌萎缩症2L型家系有关。为此，他们建立了一个人小热休克蛋白8基因K141N突变的转基因小鼠模型，用于周围神经单基因遗传病腓骨肌萎缩症的研究。结果发现转基因小鼠6个月时后肢肌肉力量及运动功能减弱，且坐骨神经轴突形态和功能都出现退化，而髓鞘未出现病变。故作者认为，该模型可以作为研究腓骨肌萎缩症2L型发病机制的K141NHSPB8转基因小鼠模型。相关文献发表于《中国神经再生研究（英文版）》杂志2014年2月第4期。

K141NHSPB8转基因小鼠远端坐骨神经中轴突的数量比野生型明显减少

Article: " A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L," by Ruxu Zhang1, Fufeng Zhang2, Xiaobo Li1, Shunxiang Huang1, Xiaohong Zi1, Ting Liu1, Sanmei Liu1, Xuning Li1, Kun Xia3, Qian Pan3, Beisha Tang2, 3 (1 Department of Neurology, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 2 Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 3 National Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan Province, China)

Zhang RX, Zhang FF, Li XB, Huang SX, Zi XH, Liu T, Liu SM, Li XN, Xia K, Pan Q, Tang BS. A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L. Neural Regen Res. 2014;9(4):413-419.

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A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L

Dr. Ruxu Zhang and colleagues from Third Xiangya Hospital, Central South University in China previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. Therefore, they generated a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. The K141NHSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the

中国中南大学湘雅三医院张如旭博士所在团队既往研究发现,小热休克蛋白8的K141N突变与中国腓骨肌萎缩症2L型家系有关。为此,他们建立了一个人小热休克蛋白8基因K141N突变的转基因小鼠模型,用于周围神经单基因遗传病腓骨肌萎缩症的研究。结果发现转基因小鼠6个月时后肢肌肉力量及运动功能减弱,且坐骨神经轴突形态和功能都出现退化,而髓鞘未出现病变。

SICENCE新闻发布 作者：张如旭 稿号：nrr-15-13

compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141NHSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings, published in the Neural Regeneration Research (Vol. 9, No. 4, 2014), indicate that the K141NHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.

Toluidine blue staining of semithin sciatic nerve sections of 6-month-old K141NHSPB8 Tg showed a decrease in the number of axons. HSPB8: Heat shock protein B.

Article: " A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L," by Ruxu Zhang1, Fufeng Zhang2, Xiaobo Li1, Shunxiang Huang1, Xiaohong Zi1, Ting Liu1, Sanmei Liu1, Xuning Li1, Kun Xia3, Qian Pan3, Beisha Tang2, 3 (1 Department of Neurology, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 2 Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 3 National Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan Province, China)

Zhang RX, Zhang FF, Li XB, Huang SX, Zi XH, Liu T, Liu SM, Li XN, Xia K, Pan Q, Tang BS. A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L. Neural Regen Res. 2014;9(4):413-419.