Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for amyotrophic lateral sclerosis and frontotemporal dementia (strand specific RNA-seq)


ABSTRACT: Purpose: The purpose of this experiment is to identify expression changes after ASO-dependent depletion of mouse C9orf72 in the spinal cord of wild-type C57Bl/6 female mice. Methods: Strand specific RNA-seq was performed using RNAs extracted from spinal cord of C57Bl/6 mice two weeks after intracerebroventricular stereotactic injection of saline (n=3), a control ASO (n=3) or an ASO targeting mouse C9orf72 (n=3). C9orf72 RNA levels were reduced to approximately 30% of control levels in spinal cords from mice treated with the C9orf72 ASO. Results: Statistical comparison of RPKM values between RNAs from C9orf72 and control ASO treated animals or C9orf72 and saline treated samples revealed that only 12 genes were consistently upregulated (defined by P<0.05 adjusted for multiple testing) and 12 genes including C9orf72 were downregulated (defined by P<0.05 adjusted for multiple testing). Conclusions: Only few RNA expression changes were identified in the spinal cord following reduction of C9orf72. Use of strand specific RNA-seq to test the consequences of C9orf72 loss of function in mouse spinal cord.

ORGANISM(S): Mus musculus

SUBMITTER: Gene Yeo 

PROVIDER: E-GEOD-51685 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration.

Lagier-Tourenne Clotilde C   Baughn Michael M   Rigo Frank F   Sun Shuying S   Liu Patrick P   Li Hai-Ri HR   Jiang Jie J   Watt Andrew T AT   Chun Seung S   Katz Melanie M   Qiu Jinsong J   Sun Ying Y   Ling Shuo-Chien SC   Zhu Qiang Q   Polymenidou Magdalini M   Drenner Kevin K   Artates Jonathan W JW   McAlonis-Downes Melissa M   Markmiller Sebastian S   Hutt Kasey R KR   Pizzo Donald P DP   Cady Janet J   Harms Matthew B MB   Baloh Robert H RH   Vandenberg Scott R SR   Yeo Gene W GW   Fu Xiang-Dong XD   Bennett C Frank CF   Cleveland Don W DW   Ravits John J  

Proceedings of the National Academy of Sciences of the United States of America 20131029 47


Expanded hexanucleotide repeats in the chromosome 9 open reading frame 72 (C9orf72) gene are the most common genetic cause of ALS and frontotemporal degeneration (FTD). Here, we identify nuclear RNA foci containing the hexanucleotide expansion (GGGGCC) in patient cells, including white blood cells, fibroblasts, glia, and multiple neuronal cell types (spinal motor, cortical, hippocampal, and cerebellar neurons). RNA foci are not present in sporadic ALS, familial ALS/FTD caused by other mutations  ...[more]

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