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| Status |
Public on Apr 14, 2017 |
| Title |
Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in mouse. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1-/y) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.
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| Overall design |
6 samples RNA-seq. 3 kos, 3wts.
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| Contributor(s) |
Ung D, Iacono G, Méziane H, Stunnenberg HG, Vincent JB, Kasri NN, Hérault Y, Laumonnier F |
| Citation(s) |
28416808 |
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| Submission date |
Apr 14, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
giovanni iacono |
| Organization name |
CNAG,Centro Nacional de Análisis Genómico
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| Department |
single cell sequencing
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| Lab |
Holger Heyn
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| Street address |
Baldiri Reixac, 4
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| City |
Barcelona |
| State/province |
Spain |
| ZIP/Postal code |
08028 |
| Country |
Spain |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA318532 |
| SRA |
SRP073338 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80312_Table_S3.xlsx |
4.7 Mb |
(ftp)(http) |
XLSX |
| GSE80312_Table_S4.xlsx |
90.0 Kb |
(ftp)(http) |
XLSX |
| GSE80312_Table_S5.txt.gz |
30.2 Kb |
(ftp)(http) |
TXT |
| GSE80312_Table_S6.txt.gz |
45.2 Kb |
(ftp)(http) |
TXT |
| GSE80312_Table_S7.xlsx |
11.2 Mb |
(ftp)(http) |
XLSX |
| GSE80312_Table_S8.xlsx |
11.3 Mb |
(ftp)(http) |
XLSX |
| GSE80312_Table_S9.xlsx |
513.1 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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