Idioma:

Loss of ERLIN2 function leads to juvenile primary lateral sclerosis

Al-Saif, Amr ; Bohlega, Saeed ; Al-Mohanna, Futwan

Annals of neurology, 2012-10, Vol.72 (4), p.510-516 [Periódico revisado por pares]

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Texto completo disponível

Citações Citado por

Enviar para

Título:
Loss of ERLIN2 function leads to juvenile primary lateral sclerosis
Autor: Al-Saif, Amr ; Bohlega, Saeed ; Al-Mohanna, Futwan
Assuntos: Adolescent ; Amyotrophic lateral sclerosis ; Biological and medical sciences ; Cell Count ; Cells, Cultured ; Child ; Child, Preschool ; Chromosome Mapping ; Chromosomes, Human, Pair 8 - genetics ; DNA - genetics ; DNA - isolation & purification ; Endoplasmic Reticulum-Associated Degradation - genetics ; Endoplasmic Reticulum-Associated Degradation - physiology ; Female ; Genes ; Humans ; Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent - metabolism ; Infant ; Inositol 1,4,5-Trisphosphate Receptors - metabolism ; Lipids ; Male ; Medical sciences ; Membrane Proteins - genetics ; Membrane Proteins - physiology ; Motor Neuron Disease - genetics ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Mutation ; Neurology ; Real-Time Polymerase Chain Reaction ; RNA Interference - physiology ; RNA Splice Sites - genetics ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Signal Transduction - genetics ; Signal Transduction - physiology ; Transfection
É parte de: Annals of neurology, 2012-10, Vol.72 (4), p.510-516
Notas: istex:99978494C314D095028C323B9CF5EB8F377BFB23
ark:/67375/WNG-FL5KD1MT-K
ArticleID:ANA23641
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Article-2
ObjectType-Feature-1
Descrição: Objective: Primary lateral sclerosis (PLS) is a motor neuron disorder that exclusively affects upper motor neurons leading to their degeneration. Mutations in the ALS2 gene encoding the protein Alsin have been described previously in the juvenile form of the disease. In this study, we identify mutation of the ERLIN2 gene in juvenile PLS patients and describe an in vitro model for loss of ERLIN2 function. Methods: Single nucleotide polymorphism arrays were used for homozygosity mapping. DNA sequencing of candidate genes was used to detect the underlying mutation. Level of ERLIN2 mRNA was measured by quantitative real time polymerase chain reaction. Knocking down ERLIN2 in NSC34 cells was accomplished by short‐hairpin RNA interference. Results: We identified a splice junction mutation in the ERLIN2 gene—a component of the endoplasmic reticulum (ER) lipid rafts—that resulted in abnormal splicing of ERLIN2 transcript and nonsense‐mediated decay of ERLIN2 mRNA. Knocking down ERLIN2 in NSC34 cells suppressed their growth in culture. Interpretation: Recently, we found that mutation of SIGMAR1, a component of ER lipid rafts, leads to juvenile amyotrophic lateral sclerosis. The identification of mutation in another component of the ER lipid rafts in juvenile PLS patients emphasizes their role in motor neuron function. Furthermore, the discovered effect of ERLIN2 loss on cell growth may advance understanding of the mechanism behind motor neuron degeneration in PLS. ANN NEUROL 2012;72:510–516
Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Idioma: Inglês

Links

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Loss of ERLIN2 function leads to juvenile primary lateral sclerosis

Al-Saif, Amr ; Bohlega, Saeed ; Al-Mohanna, Futwan

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Buscando em bases de dados remotas. Favor aguardar.