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Spinal Muscular Atrophy: New and Emerging Insights from Model Mice

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Abstract

Spinal muscular atrophy (SMA) is a common and often fatal neurodegenerative disease that primarily afflicts infants and young children. SMA is caused by abnormally low levels of the survival motor neuron (SMN) protein resulting from a combination of recessively inherited mutations in the SMN1 gene and the presence of an almost identical but partially functional copy gene, SMN2. Absence of the uniquely human SMN2 gene in SMA patients has never been reported because the SMN protein is indispensable for cell survival. Modeling SMA in animals therefore poses a challenge. This review describes the different strategies used to overcome this hurdle and model SMA in mice. We highlight new and emerging insights regarding SMA gained by studying the mice and illustrate how the animals serve as important tools to understand and eventually treat the human disease.

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Acknowledgments

We are grateful to Drs. D. C. De Vivo, S. Przedborski, and C. E. Henderson for advice and to S. Patruni for critically reading this manuscript. Work in the laboratory is funded by National Institute of Neurological Disorders and Stroke (NINDS) R01 NS057482, NINDS P01 NS055923, US Department of Defense (DoD) W81XWH-09-1-0245, DoD W81XWH-08-1-0009, the Motor Neuron Center, Columbia University, and the SMA Foundation, which also was instrumental in coordinating the generation of the newer model mice.

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Department of Neurology, Columbia University Medical Center, 630 West 178th Street, Room 5-422, New York, NY, 10032, USA

    Gyu-Hwan Park, Shingo Kariya & Umrao R. Monani

  2. Department of Pathology & Cell Biology, Columbia University Medical Center, 630 West 178th Street, Room 5-422, New York, NY, 10032, USA

    Umrao R. Monani

  3. Center for Motor Neuron Biology and Disease, Columbia University Medical Center, 630 West 178th Street, Room 5-422, New York, NY, 10032, USA

    Gyu-Hwan Park, Shingo Kariya & Umrao R. Monani

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  1. Gyu-Hwan Park
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Correspondence to Umrao R. Monani.

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Park, GH., Kariya, S. & Monani, U.R. Spinal Muscular Atrophy: New and Emerging Insights from Model Mice. Curr Neurol Neurosci Rep 10, 108–117 (2010). https://doi.org/10.1007/s11910-010-0095-5

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