Spinal muscular atrophy: new and emerging insights from model mice.

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.