Anti-SMN1: Mouse SMN1 Antibody

BACKGROUND The human survival motor neuron (SMN) protein is a ubiquitously expressed protein of 294 amino acids that migrates with a molecular weight of approximately 38 kDa. The SMN protein is found in many cells within the central and peripheral nervous system and is abundant in normal motor neurons. SMN protein is significantly reduced in spinal muscular atrophy (SMA) affected tissue and primary cell cultures. Several functions of the SMN protein have been described. The most completely characterized roles for SMN are in snRNP biogenesis. In this function, SMN is found in a “core” complex with several other proteins called gemins (Gemin 2-8) and unrip. A distinguishing feature of the SMN protein is that it localizes to punctate nuclear bodies originally identified as “gems”. The number of gems in SMA patient-derived fibroblasts and tissues is linked to disease severity. In most cell lines and tissues, the structures originally identified as gems are coincident with Cajal bodies; structures that are highly enriched for RNA processing components including snRNPs and the Cajal body-marker protein p80 coilin. SMN is also proposed to function in the transportation of β-actin mRNA in neurites, raising the possibility that SMN is involved in the axonal localization and transport of specific mRNA species.¹

Two most identical copies of SMN gene, telomeric SMN (SMN1) and centromeric SMN (SMN2) have been identified. The SMN1 gene resides in a duplicated region of chromosome 5q13 telomeric to the near identical homolog SMN2. More than 90% of the functional SMN protein is contributed by SMN1. Comparably SMN2 produces only a small fraction of SMN due to a point mutation in exon 7 that disrupts an exon splice enhancer site, preventing normal post-transcription processing.² In the general population the copy number of SMN1 and SMN2 genes varies. Published information suggests that 85%-95% of the population has one copy of the SMN1 gene per allele; however, individuals with more than one copy per allele have been identified. SMN2, a nearly identical paralog of SMN1, is present in the human genome as part of an inverted duplication on 5q13. SMN2 expresses limited amounts of functional, full-length SMN protein, which is apparently sufficient for normal activity in most cell types but not in motor neurons. SMN2 is efficiently transcribed but cannot fully compensate for the loss of SMN1, because a translationally silent, single-nucleotide transition in SMN2 at position 6 of exon 7 (c6t) causes predominant exon 7 skipping and results in an unstable protein (SMNΔ7) with a different C-terminus. Spinal Muscular Atrophy (SMA) is a common autosomal recessive neuromuscular disorder caused by the loss of α-motor neurons in the spinal cord. The most frequent mutation is the biallelic deletion of exon 7 of the SMN1 gene. However, the severity of the disease is mainly determined by the copy number of SMN2.³ Genetic conversion of an SMN2 gene to SMN1 maybe a novel approach to the treatment of spinal muscular atrophy.⁴
 

REFERENCES  

1. Burglen, L. et al: Genomics 32:479-82, 1996
2. Qu, Y.J. et al: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 28:121-6, 2001
3. Sun, Y. et al: Human Mutation 25:64-71, 2005
4. DiMatteo, D. et al: Exp. Cell Res. 314:878-86, 2008