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C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits

Koppers, Max ; Blokhuis, Anna M. ; Westeneng, Henk-Jan ; Terpstra, Margo L. ; Zundel, Caroline A. C. ; Vieira de Sá, Renata ; Schellevis, Raymond D. ; Waite, Adrian J. ; Blake, Derek J. ; Veldink, Jan H. ; van den Berg, Leonard H. ; Pasterkamp, R. Jeroen

Annals of neurology, 2015-09, Vol.78 (3), p.426-438 [Periódico revisado por pares]

United States: Blackwell Publishing Ltd

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Título:
C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits
Autor: Koppers, Max ; Blokhuis, Anna M. ; Westeneng, Henk-Jan ; Terpstra, Margo L. ; Zundel, Caroline A. C. ; Vieira de Sá, Renata ; Schellevis, Raymond D. ; Waite, Adrian J. ; Blake, Derek J. ; Veldink, Jan H. ; van den Berg, Leonard H. ; Pasterkamp, R. Jeroen
Assuntos: Amino Acid Sequence ; Amyotrophic lateral sclerosis ; Animals ; C9orf72 Protein ; Gene Knockout Techniques ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Molecular Sequence Data ; Motor Neuron Disease - genetics ; Motor Neuron Disease - pathology ; Motor Neurons - pathology ; Nerve Degeneration - genetics ; Nerve Degeneration - pathology ; Proteins - genetics ; Rodents
É parte de: Annals of neurology, 2015-09, Vol.78 (3), p.426-438
Notas: istex:DF2EC785D1464EEBDCA8630B941211DA2C404A37
Van Meer Stichting, Netherlands ALS Foundation
ark:/67375/WNG-FFL5F69H-9
Prinses Beatrix Spierfonds
European Community Health Seventh Framework Program - No. 259867
Thierry Latran Foundation
ArticleID:ANA24453
Netherlands Organization for Health Research and Development
Motor Neurone Disease Association - No. Blake/Mar12/6088
The copyright line for this article was changed on 21 August 2015 after original online publication.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Objective How hexanucleotide (GGGGCC) repeat expansions in C9ORF72 cause amyotrophic lateral sclerosis (ALS) remains poorly understood. Both gain‐ and loss‐of‐function mechanisms have been proposed. Evidence supporting these mechanisms in vivo is, however, incomplete. Here we determined the effect of C9orf72 loss‐of‐function in mice. Methods We generated and analyzed a conditional C9orf72 knockout mouse model. C9orf72fl/fl mice were crossed with Nestin‐Cre mice to selectively remove C9orf72 from neurons and glial cells. Immunohistochemistry was performed to study motor neurons and neuromuscular integrity, as well as several pathological hallmarks of ALS, such as gliosis and TDP‐43 mislocalization. In addition, motor function and survival were assessed. Results Neural‐specific ablation of C9orf72 in conditional C9orf72 knockout mice resulted in significantly reduced body weight but did not induce motor neuron degeneration, defects in motor function, or altered survival. Interpretation Our data suggest that C9orf72 loss‐of‐function, by itself, is insufficient to cause motor neuron disease. These results may have important implications for the development of therapeutic strategies for C9orf72‐associated ALS. Ann Neurol 2015;78:426–438
Editor: United States: Blackwell Publishing Ltd
Idioma: Inglês

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C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits

Koppers, Max ; Blokhuis, Anna M. ; Westeneng, Henk-Jan ; Terpstra, Margo L. ; Zundel, Caroline A. C. ; Vieira de Sá, Renata ; Schellevis, Raymond D. ; Waite, Adrian J. ; Blake, Derek J. ; Veldink, Jan H. ; van den Berg, Leonard H. ; Pasterkamp, R. Jeroen

United States: Blackwell Publishing Ltd

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