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SMN expression is required in motor neurons to rescue electrophysiological deficits in the SMNΔ7 mouse model of SMA.
McGovern, Vicki L; Iyer, Chitra C; Arnold, W David; Gombash, Sara E; Zaworski, Phillip G; Blatnik, Anton J; Foust, Kevin D; Burghes, Arthur H M.
Afiliación
  • McGovern VL; Department of Molecular and Cellular Biochemistry, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
  • Iyer CC; Department of Molecular and Cellular Biochemistry, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
  • Arnold WD; Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA Department of Physical Medicine and Rehabilitation, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA Department of Neuroscience, The Ohio State University Wexner Medical Center,
  • Gombash SE; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA and.
  • Zaworski PG; PharmOptima, LLC, Portage, MI 49002, USA.
  • Blatnik AJ; Department of Molecular and Cellular Biochemistry, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
  • Foust KD; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA and.
  • Burghes AH; Department of Molecular and Cellular Biochemistry, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA burghes.1@osu.edu.
Hum Mol Genet ; 24(19): 5524-41, 2015 Oct 01.
Article en En | MEDLINE | ID: mdl-26206889
Proximal spinal muscular atrophy (SMA) is the most frequent cause of hereditary infant mortality. SMA is an autosomal recessive neuromuscular disorder that results from the loss of the Survival Motor Neuron 1 (SMN1) gene and retention of the SMN2 gene. The SMN2 gene produces an insufficient amount of full-length SMN protein that results in loss of motor neurons in the spinal cord and subsequent muscle paralysis. Previously we have shown that overexpression of human SMN in neurons in the SMA mouse ameliorates the SMA phenotype while overexpression of human SMN in skeletal muscle had no effect. Using Cre recombinase, here we show that either deletion or replacement of Smn in motor neurons (ChAT-Cre) significantly alters the functional output of the motor unit as measured with compound muscle action potential and motor unit number estimation. However ChAT-Cre alone did not alter the survival of SMA mice by replacement and did not appreciably affect survival when used to deplete SMN. However replacement of Smn in both neurons and glia in addition to the motor neuron (Nestin-Cre and ChAT-Cre) resulted in the greatest improvement in survival of the mouse and in some instances complete rescue was achieved. These findings demonstrate that high expression of SMN in the motor neuron is both necessary and sufficient for proper function of the motor unit. Furthermore, in the mouse high expression of SMN in neurons and glia, in addition to motor neurons, has a major impact on survival.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Atrofia Muscular Espinal / Músculo Esquelético / Proteína 1 para la Supervivencia de la Neurona Motora / Neuronas Motoras Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Atrofia Muscular Espinal / Músculo Esquelético / Proteína 1 para la Supervivencia de la Neurona Motora / Neuronas Motoras Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido