Spinal muscle atrophy (SMA) is an autosomal recessive neurodegenerative disease which is characterized by the loss of alpha motor neurons resulting in progressive muscle atrophy. Reduced amount of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene is the cause of SMA. A potential treatment strategy for SMA is to upregulate levels of SMN protein originat...

Spinal muscular atrophy (SMA) is an autosomal recessive disorder that is characterized by the degeneration of the motor neurons of the spinal cord leading to muscle atrophy. SMA is a result of a loss-of-function of the gene survival motor neuron-1 (SMN1). We have chosen to generate a transgenic swine model of SMA for the development and testing of therapeutics and evaluation of toxicology. To t...

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1 Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophil...

Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons of the spinal cord associated with muscle paralysis and caused by mutations of the survival motor neuron gene (SMN). To determine whether SMN gene defect in skeletal muscle might have a role in SMA pathogenesis, deletion of murine SMN exon 7, the most frequent mutation found in SMA, has been restricted to skeletal m...

Spinal muscular atrophy (SMA) is caused by homozygous mutation or deletion of the SMN1 gene encoding survival of motor neuron (SMN) protein, resulting in the selective loss of -motor neurons. Humans typically have one or more copies of the SMN2 gene, the coding region of which is nearly identical to SMN1, except that a point mutation causes splicing out of exon 7 and production of a largely non...

Spinal muscular atrophy (SMA) is an inherited neuro-muscular disease characterized by specific degeneration of spinal cord anterior horn cells and subsequent muscle atrophy. Survival motor neuron ( SMN ), located on chromosome 5q13, is the SMA-determining gene. In the nucleus, SMN is present in large foci called gems, the function of which is not yet known, while cytoplasmic SMN has been implic...

Low levels of the survival motor neuron protein (SMN) cause the disease spinal muscular atrophy. A primary characteristic of this disease is motoneuron dysfunction and paralysis. Understanding why motoneurons are affected by low levels of SMN will lend insight into this disease and to motoneuron biology in general. Motoneurons in zebrafish smn mutants develop abnormally; however, it is unclear ...

Spinal muscular atrophy (SMA) is a primary genetic cause of infant mortality due to mutations in the Survival Motor Neuron (SMN) 1 gene. No cure is available. Antisense oligonucleotides (ASOs) aimed at increasing SMN levels from the paralogous SMN2 gene represent a possible therapeutic strategy. Here, we tested in SMA human induced pluripotent stem cells (iPSCs) and iPSC-differentiated motor ne...

Significant strides have been made during the past decade in the understanding of the molecular mechanisms that lead to the autosomal recessive motor neuron disease spinal muscular atrophy. Genetic studies revealed that spinal muscular atrophy is caused by mutation of the telomeric copy of the survival motor neuron gene ( SMN1), with all patients retaining at least one copy of the centromeric f...

Spinal muscular atrophy (SMA) is a devastating motor neuron disease caused by mutations of the survival motor neuron 1 (SMN1) gene. SMN2, a paralogous gene to SMN1, can partially compensate for the loss of SMN1. On the basis of age at onset, highest motor function and SMN2 copy numbers, childhood-onset SMA can be divided into three types (SMA I-III). An inverse correlation was observed between ...