These results identify critical domains within the SMN protein and have an impact on our understanding of the SMN protein with regards to SMA as well as cellular biology.
A deficiency of the SMN protein results in the inherited neurodegenerative condition SMA (spinal muscular atrophy), a leading cause of infant mortality specifically affecting spinal motor neurons.
We report here the finding of abnormal Golgi apparatus morphology in motor neuron like cells depleted of SMN as well as Golgi apparatus morphology in SMA patient fibroblasts.
Infantile spinal muscular atrophy (SMA) caused by homozygous SMN1 gene deletions/mutations is characterized by neuronal loss and axonopathy of motor neurons.
Reduction of the survival of motor neurons (SMN) protein levels causes the motor neuron degenerative disease spinal muscular atrophy, the severity of which correlates with the extent of reduction in SMN.
We used the SMN∆7 mouse model of SMA to investigate the cellular reorganization of polyadenylated mRNAs associated with the splicing dysfunction in MNs.
Of the 12 neuromuscular studies exclusively on spinal muscular atrophy type 1 (SMA1), six (50%) reported decreased hospitalizations and nine (75%) reported on mortality outcomes.
Antisense therapy targeting SMN2 which leads to SMN protein expression has been at the forefront of research when it comes to developing a feasible therapy for treating SMA.
We performed a systematic analysis of SMN expression in primary fibroblasts and EBV-transformed lymphoblasts from seven SMA patients with varying clinical severity and different SMN1 genotypes to determine expression differences in two accessible tissues (skin and blood).
Linkage studies, as well as the analysis of the SMN gene, recognised that SMA variants (with severe arthogryposis or cerebellar or diaphragmatic involvement) are not linked to chromosome 5q markers.
Deletion or mutation of SMN1 coupled with the inability of SMN2 to compensate for the loss of SMN1 due to exon 7 skipping causes spinal muscular atrophy (SMA), one of the leading genetic diseases of children.
In contrast to other neurodegenerative disorders, SMA is a genetically homozygous autosomal recessive disease that is caused by deficiency of the survival motor neuron (SMN) protein.
The assay has been optimized and tested in 48 healthy controls, 20 known patients with SMA, 12 carriers (one SMN1 copy), and 8 amniotic fluids suspected of having SMA for whom we had determined the SMN1/SMN2 deletion by an additional PCR-RFLP method.
Importantly, an SMA-causing mutation in the Tudor domain of SMN completely abolished translational repression, a strong indication for the functional significance of this novel SMN activity in the pathology.