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| Status |
Public on Apr 09, 2018 |
| Title |
A Upf3b-mutant mouse model with behavioral and neurogenesis defects |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, causes intellectual disability (ID) and are strongly associated with autism spectrum (ASD), attention deficit hyperactivity disorder (ADHD), and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and they require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B- regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation, and disease. We suggest that Upf3b-null mice serves as a novel model system to decipher cellular and molecular defects underlying ID and neuro-developmental disorders.
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| Overall design |
Analyzing differential gene expression in frontal cortex of wild type versus Upf3b-null mice
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| Contributor(s) |
Chousal J, Jones SH |
| Citation(s) |
28948974 |
| Submission date |
May 19, 2017 |
| Last update date |
Sep 15, 2022 |
| Contact name |
Heidi Cook-Andersen |
| E-mail(s) |
hcookandersen@ucsd.edu
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| Organization name |
University of California, San Diego
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| Department |
Department of Reproductive Medicine
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| Street address |
2880 Torrey Pines Scenic Drive, Rm 4811
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| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA387301 |
| SRA |
SRP107560 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99112_UPF3B_readcounts.txt.gz |
437.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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