Spinal muscular atrophy is a devastating disease that is characterized by degeneration and death of a specific subclass of motor neurons in the anterior horn of the spinal cord. Although the gene responsible, survival motor neuron 1 (SMN1), was identified 20 years ago, it has proven difficult to investigate its effects in vivo. Consequently, a number of key questions regarding the molecular and...

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 ...

Humans have two near identical copies of the survival of motor neuron (SMN) gene, SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to an inhibitory mutation at position 6 (C6U mutation in transcript) of exon 7. We have recently shown that C6U creates an extended inhibitory context (Exinct) that causes skipping of exon 7 in SMN2. Previous s...

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with dysfunctional α-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss (∼95% of SMA cases) or mutation (∼5% of SMA cases) of the survival motor neuron 1 gene SMN1. As the product of SMN1, SMN is a component of the SMN complex, and is also involved in the biosynthesis of the small nuclear rib...

Spinal muscular atrophy (SMA) describes a group of disorders associated with spinal motor neuron loss. In this review we provide an update regarding the most common form of SMA, proximal or 5q-SMA, and discuss the contemporary approach to diagnosis and treatment. Electromyography and muscle biopsy features of denervation were once the basis for diagnosis, but molecular testing for homozygous de...

Mutations in the SMN1 (survival motor neuron 1) gene cause spinal muscular atrophy (SMA). We now show that SMN protein, the SMN1 gene product, interacts directly with the tumor suppressor protein, p53. Pathogenic missense mutations in SMN reduce both self-association and p53 binding by SMN, and the extent of the reductions correlate with disease severity. The inactive, truncated form of SMN pro...

Although zebrafish is used to model human diseases through mutational and morpholino-based knockdown approaches, there are currently no robust transgenic knockdown tools. Here we investigate the knockdown efficiency of three synthetic miRNA-expressing backbones and show that these constructs can downregulate a sensor transgene with different degrees of potency. Using this approach, we reproduce...

Hereditary spinal muscular atrophy is a motor neuron disorder characterized by muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord. Initially, the disease was considered purely as an autosomal recessive condition caused by loss-of-function SMN1 mutations on 5q13. Recent developments in next generation sequencing technologies, however, have unveiled a gr...

We report subarcsecond images of the high-mass star forming region Onsala 1 (ON 1) made with the Submillimeter Array (SMA) at 0.85 mm and the Very Large Array at 1.3 cm and 3.6 cm. ON 1 is one of the smallest ultracompact H II regions in the Galaxy and exhibits various star formation signposts. With our VLA and SMA observations, two new cm-wave sources and five sub-mm dust sources, respectively...

Although the serotonergic system and htr1A have been studied extensively, little is known about the canine serotonin receptor 1A. We are interested in this receptor in the dog because it is likely to be involved in behavioral disorders such as anxiety. Therefore, we isolated a canine bacterial artificial chromosome (BAC) clone containing htr1A, and, with the help of this clone, the complete can...