Neuromuscular defects and breathing disorders in a new mouse model of spinal muscular atrophy

作者：Michaud Magali; Arnoux Thomas; Bielli Serena; Durand Estelle; Rotrou Yann; Jablonka Sibylle; Robert Fabrice; Giraudon Paoli Marc; Riessland Markus; Mattei Marie Genevieve; Andriambeloson Emile; Wirth Brunhilde; Sendtner Michael; Gallego Jorge; Pruss Rebecca M; Bordet Thierry^*

来源：Neurobiology of Disease, 2010, 38(1): 125-135.

DOI：10.1016/j.nbd.2010.01.006

• Spinal muscular atrophy
• Motor neuron disease
• Mouse model
• Survival motor neuron gene
• Neurodegeneration
• Behavior
• Breathing disorders
• Neuromuscular junction
• Development

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.

• 出版日期2010-4