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Series GSE135075 Query DataSets for GSE135075
Status Public on Jul 30, 2020
Title FUS-mediated dysregulation of Sema5a, an autism-related gene, in FUS mice with hippocampus-dependent cognitive deficits
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Pathological FUS inclusions are found in 10% of patients with frontotemporal dementia (FTD) and those with amyotrophic lateral sclerosis (ALS) carrying FUS mutations. Current work indicates that FUS mutations may incur gain-of-toxic functions to drive ALS pathogenesis. However, how FUS dysfunction may affect cognition remains elusive. Using a mouse model expressing wild-type human FUS mimicking the endogenous expression pattern and level within the central nervous system, we found that they developed hippocampus-mediated cognitive deficits accompanied by an age-dependent reduction in spine density and long-term potentiation (LTP) in their hippocampus. However, there were no apparent FUS aggregates, nuclear envelope defects and cytosolic FUS accumulation. These suggest that these proposed pathogenic mechanisms may not be the underlying causes for the observed cognitive deficits. Unbiased transcriptomic analysis identified expression changes in a small set of genes with preferential expression in the neurons and oligodendrocyte lineage cells. Of these, we focused on Sema5a, a gene involved in axon guidance, spine dynamics, Parkinson’s disease and autism spectrum disorders. Critically, FUS binds directly to Sema5a mRNA and regulates Sema5a expression in a FUS-dose-dependent manner. Taken together, our data suggest that FUS-driven Sema5a deregulation may underlie the cognitive deficits in FUS transgenic mice.
Overall design Differential gene expression analysis of 12-month-old prnp-hFUSWT mice hippocampus
Contributor(s) Wan YH, Chang J, Tyan S, Yen Y, Lim K, Tan BS, Ong J, Tucker-Kellogg G, Wong P, Koo E, Ling S
Citation(s) 31509188
Submission date Jul 30, 2019
Last update date Sep 05, 2020
Contact name Shuo-Chien Ling
Phone +65 66013645
Organization name National University of Singapore
Department Physiology
Lab Shuo-Chien Ling
Street address 12 Science Drive 2, MD1, 16-03-H
City Singapore
State/province Singapore
ZIP/Postal code 117549
Country Singapore
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (6)
GSM3984864 Nontransgenic mouse ID 441 [RMH1552]
GSM3984865 Nontransgenic mouse ID 442 [RMH1553]
GSM3984866 Nontransgenic mouse ID 147 [RMH1554]
BioProject PRJNA557350
SRA SRP216803

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Supplementary file Size Download File type/resource
GSE135075_rawCounts.csv.gz 299.3 Kb (ftp)(http) CSV
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