The disease is mainly caused by low level of the survival motor neuron (SMN) protein, which is coded by two genes, namely SMN1 and SMN2, but leads to selective spinal motor neuron degeneration when SMN1 gene is deleted or mutated.
Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy.
Interestingly, smn1 knockdown in motor neurons also induced severe late-onset phenotypes including scoliosis-like body deformities, weight loss, muscle atrophy and, seen for the first time in zebrafish, reduction in the number of motor neurons, indicating motor neuron degeneration.
Although the genetic cause of SMA has been mapped to the Survival Motor Neuron1 (SMN1) gene, mechanisms underlying selective motor neuron degeneration in SMA remain largely unknown.
Although the SMN complex is essential for assembly of spliceosomal U small nuclear RNPs, it is still not understood why reduced levels of the SMN protein specifically cause motor neuron degeneration.
The reason why reduced levels of the ubiquitously expressed SMN protein lead to specific motor neuron degeneration without affecting other cell types is still not understood.
Here we show that a 46% reduction of Smn protein levels in the spinal cord of Smn heterozygous mice leads to a marked loss of the cytoplasmic Smn pool and motor neuron degeneration resembling spinal muscular atrophy type 3.
The Survival Motor Neuron (SMN) gene shows deletions in the majority of patients with Spinal Muscular Atrophy (SMA), a disease of motor neuron degeneration.