PXD019335 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A new Knock-in mouse model of SCA14 with increased PKCγ activity induces a SCA-like phenotype with perturbed Purkinje cell maturation and ataxic motor behavior |
Description | Spinocerebellar ataxias (SCAs) are a group of cerebellar diseases characterized by loss and dysfunction of Purkinje cells and Spinocerebellar ataxia type 14 (SCA14) is caused by missense mutations or deletions in the Protein kinase C γ (PKCγ) gene. Until now, more than 40 different mutations or deletions in the PKCγ gene have been found in SCA14 patients. Many of these mutations have been shown to have an increased enzymatic activity in cell-based assays, but there is also evidence that the mutations may result in inefficient activation of downstream signalling pathways compatible with a loss of function. Therefore, it is still unclear how mutant PKCγ may cause the disease. We have previously generated a transgenic SCA14 mouse model with a human SCA14 mutation in the kinase domain. This transgenic mouse shows mild ataxia and abnormal Purkinje cell dendritic development with a morphology indistinguishable from that of PKC activator treated Purkinje cells, indicating that the PKCγ with this kinase domain mutation has indeed increased biological activity. In order to confirm that increased PKC activity in vivo perturbs Purkinje cell maturation and induces ataxia we have now created a new knock-in mouse model with a missense mutation in the PKCγ pseudosubstrate domain keeping the PKCγ protein in the open active conformation. This knock-in mouse shows indeed abnormal Purkinje cell maturation and ataxia, even in a heterozygous state corresponding to the human disease situation. Our findings confirm that constitutive activation of PKCγ is one way to induce a phenotype corresponding to human spinocerebellar ataxia. |
HostingRepository | PRIDE |
AnnounceDate | 2022-02-24 |
AnnouncementXML | Submission_2022-02-24_04:36:41.270.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD019335 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Alexander Schmidt |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | Phospho; TMT6plex; phosphorylated residue; Oxidation; Acetyl; Carbamidomethyl |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-05-21 22:46:53 | ID requested | |
⏵ 1 | 2022-02-24 04:36:42 | announced | |
Publication List
Shimobayashi E, Kapfhammer JP, Shows Perturbed Purkinje Cell Maturation and Ataxic Motor Behavior. J Neurosci, 41(9):2053-2068(2021) [pubmed] |
Keyword List
submitter keyword: SCA, PKC gamma, Phosphoproteomics |
Contact List
Alexander Schmidt |
contact affiliation | Proteomics Core Facility, Biozentrum, University of Basel, Switzerland |
contact email | alex.schmidt@unibas.ch |
lab head | |
Alexander Schmidt |
contact affiliation | Proteomics Core Facility |
contact email | alex.schmidt@unibas.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019335
- Label: PRIDE project
- Name: A new Knock-in mouse model of SCA14 with increased PKCγ activity induces a SCA-like phenotype with perturbed Purkinje cell maturation and ataxic motor behavior