The survival motor neuron protein in spinal muscular atrophy

Daniel D. Coovert, Thanh T. Le, Patricia E. McAndrew, John Strasswimmer, Thomas O. Crawford, Jerry R. Mendell, Susan E. Coulson, Elliot Androphy, Thomas W. Prior, Arthur H M Burghes

Research output: Contribution to journalArticle

523 Citations (Scopus)

Abstract

The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non-SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.

Original languageEnglish (US)
Pages (from-to)1205-1214
Number of pages10
JournalHuman Molecular Genetics
Volume6
Issue number8
DOIs
StatePublished - Aug 1997
Externally publishedYes

Fingerprint

Spinal Muscular Atrophy
Motor Neurons
Proteins
Fibroblasts
Spinal Muscular Atrophies of Childhood
Spinal Cord

ASJC Scopus subject areas

  • Genetics

Cite this

Coovert, D. D., Le, T. T., McAndrew, P. E., Strasswimmer, J., Crawford, T. O., Mendell, J. R., ... Burghes, A. H. M. (1997). The survival motor neuron protein in spinal muscular atrophy. Human Molecular Genetics, 6(8), 1205-1214. https://doi.org/10.1093/hmg/6.8.1205

The survival motor neuron protein in spinal muscular atrophy. / Coovert, Daniel D.; Le, Thanh T.; McAndrew, Patricia E.; Strasswimmer, John; Crawford, Thomas O.; Mendell, Jerry R.; Coulson, Susan E.; Androphy, Elliot; Prior, Thomas W.; Burghes, Arthur H M.

In: Human Molecular Genetics, Vol. 6, No. 8, 08.1997, p. 1205-1214.

Research output: Contribution to journalArticle

Coovert, DD, Le, TT, McAndrew, PE, Strasswimmer, J, Crawford, TO, Mendell, JR, Coulson, SE, Androphy, E, Prior, TW & Burghes, AHM 1997, 'The survival motor neuron protein in spinal muscular atrophy', Human Molecular Genetics, vol. 6, no. 8, pp. 1205-1214. https://doi.org/10.1093/hmg/6.8.1205
Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR et al. The survival motor neuron protein in spinal muscular atrophy. Human Molecular Genetics. 1997 Aug;6(8):1205-1214. https://doi.org/10.1093/hmg/6.8.1205
Coovert, Daniel D. ; Le, Thanh T. ; McAndrew, Patricia E. ; Strasswimmer, John ; Crawford, Thomas O. ; Mendell, Jerry R. ; Coulson, Susan E. ; Androphy, Elliot ; Prior, Thomas W. ; Burghes, Arthur H M. / The survival motor neuron protein in spinal muscular atrophy. In: Human Molecular Genetics. 1997 ; Vol. 6, No. 8. pp. 1205-1214.
@article{fb7740d18f2a4444ab791896b5db3793,
title = "The survival motor neuron protein in spinal muscular atrophy",
abstract = "The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non-SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.",
author = "Coovert, {Daniel D.} and Le, {Thanh T.} and McAndrew, {Patricia E.} and John Strasswimmer and Crawford, {Thomas O.} and Mendell, {Jerry R.} and Coulson, {Susan E.} and Elliot Androphy and Prior, {Thomas W.} and Burghes, {Arthur H M}",
year = "1997",
month = "8",
doi = "10.1093/hmg/6.8.1205",
language = "English (US)",
volume = "6",
pages = "1205--1214",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - The survival motor neuron protein in spinal muscular atrophy

AU - Coovert, Daniel D.

AU - Le, Thanh T.

AU - McAndrew, Patricia E.

AU - Strasswimmer, John

AU - Crawford, Thomas O.

AU - Mendell, Jerry R.

AU - Coulson, Susan E.

AU - Androphy, Elliot

AU - Prior, Thomas W.

AU - Burghes, Arthur H M

PY - 1997/8

Y1 - 1997/8

N2 - The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non-SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.

AB - The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non-SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.

UR - http://www.scopus.com/inward/record.url?scp=8544283791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8544283791&partnerID=8YFLogxK

U2 - 10.1093/hmg/6.8.1205

DO - 10.1093/hmg/6.8.1205

M3 - Article

VL - 6

SP - 1205

EP - 1214

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 8

ER -