Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we will assume that you are happy to receive all cookies and you will not see this message again. Click 'Find out more' for information on how to change your cookie settings.

Spinal muscular atrophy (SMA) is caused by mutations/deletions within the SMN1 gene and characterized by loss of lower motor neurons and skeletal muscle atrophy. SMA is clinically heterogeneous, with disease ranging from severe to mild. Here, we identify a critical threshold of Smn that dictates onset of SMA in the intermediate Smn(2B/-) mouse model. With about 15% normal level of Smn protein, Smn(2B/-) mice display reduced body weight, motor neuron loss and motor defects. Importantly, these mice are phenotype-free until P10 with a median life expectancy of 28 days. They show neuromuscular junction (NMJ) pathology with an inter-muscular differential vulnerability and an association between pre- and post-synaptic defects. Our work suggests that increasing Smn protein levels only minimally could be of significant benefit since Smn(2B/2B) mice are phenotypically normal. Further, the finding that NMJ pathology varies between severe and intermediate SMA mouse models, suggests that future therapies be adapted to the severity of SMA.

Original publication




Journal article


Neuromuscul Disord

Publication Date





263 - 276


Age Factors, Animals, Animals, Newborn, Axons, Body Weight, Brain, Bungarotoxins, Disease Models, Animal, Gait Disorders, Neurologic, Gene Expression Regulation, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Endplate, Muscle, Skeletal, Muscular Atrophy, Spinal, Nerve Degeneration, Neuromuscular Diseases, Neuromuscular Junction, Phenotype, RNA, Messenger, Reaction Time, Receptors, Cholinergic, Sensation Disorders, Spinal Cord, Survival of Motor Neuron 1 Protein