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C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model.
Huang, Cheng; Shen, Zong Rui; Huang, Jin; Sun, Shun Chang; Ma, Di; Li, Mei Yi; Wang, Zhi Kui; Zheng, Ying Chun; Zheng, Zhuo Jun; He, Fei; Xu, Xiaoyuan; Li, Ziang; Zheng, Bo Yang; Li, Yue Mao; Xu, Xiang Min; Xiong, Fu.
Afiliación
  • Huang C; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Shen ZR; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Huang J; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Sun SC; Department of Clinical Laboratory, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Ma D; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Li MY; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Wang ZK; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Zheng YC; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Zheng ZJ; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • He F; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Xu X; Experimental Teaching Center for Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Li Z; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Zheng BY; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Li YM; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Xu XM; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Xiong F; Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, Guangdong Province, P.R. China.
Hum Mol Genet ; 29(15): 2471-2480, 2020 08 29.
Article en En | MEDLINE | ID: mdl-32592472
Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Homozygous mutants of C1orf194 mice exhibited incomplete embryonic lethality, characterized by differentiation abnormalities and stillbirth on embryonic days 7.5-15.5. Heterozygous and surviving homozygous C1orf194 KO mice developed motor and sensory defects at the age of 4 months. Electrophysiologic recordings showed decreased compound muscle action potential and motor nerve conduction velocity in the sciatic nerve of C1orf194-deficient mice as a pathologic feature of dominant intermediate-type CMT. Transmission electron microscopy analysis revealed demyelination and axonal atrophy in the sciatic nerve as well as swelling and loss of mitochondrial matrix and other abnormalities in axons and Schwann cells. A histopathologic examination showed a loss of motor neurons in the anterior horn of the spinal cord and muscle atrophy. Shorter internodal length between nodes of Ranvier and Schmidt-Lanterman incisures was detected in the sciatic nerve of affected animals. These results indicate that C1orf194 KO mice can serve as an animal model of CMT with a severe dominant intermediate CMT phenotype that can be used to investigate the molecular mechanisms of the disease and evaluate the efficacy of therapeutic strategies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Charcot-Marie-Tooth / Discapacidades del Desarrollo / Sistemas de Lectura Abierta / Mortinato Límite: Animals / Humans Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Charcot-Marie-Tooth / Discapacidades del Desarrollo / Sistemas de Lectura Abierta / Mortinato Límite: Animals / Humans Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido