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.
Tthey 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 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.
This 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.
Credit: Neural Regeneration Research
These findings, published in 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.
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.