1. Neuromuscular defects and breathing disorders in a new mouse model of spinal muscular atrophy
- Author
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Magali Michaud, Thomas Arnoux, Serena Bielli, Estelle Durand, Yann Rotrou, Sibylle Jablonka, Fabrice Robert, Marc Giraudon-Paoli, Markus Riessland, Marie-Geneviève Mattei, Emile Andriambeloson, Brunhilde Wirth, Michael Sendtner, Jorge Gallego, Rebecca M. Pruss, and Thierry Bordet
- Subjects
Spinal muscular atrophy ,Motor neuron disease ,Mouse model ,Survival motor neuron gene ,Neurodegeneration ,Behavior ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein leading to muscle paralysis and respiratory failure. In mouse, introducing the human SMN2 gene partially rescues Smn-/- embryonic lethality. However current models were either too severe or nearly unaffected precluding convenient drug testing for SMA. We report here new SMN2;Smn-/- lines carrying one to four copies of the human SMN2 gene. Mice carrying three SMN2 copies exhibited an intermediate phenotype with delayed appearance of motor defects and developmental breathing disorders reminiscent of those found in severe SMA patients. Although normal at birth, at 7 days of age respiratory rate was decreased and apnea frequency was increased in SMA mice in parallel with the appearance of neuromuscular junction defects in the diaphragm. With median survival of 15 days and postnatal onset of neurodegeneration, these mice could be an important tool for evaluating new therapeutics.
- Published
- 2010
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