PXD045769

PXD045769 is an original dataset announced via ProteomeXchange.

Title	Proteome analysis of thyroid hormone transporter Mct8/Oatp1c1 deficient mice reveals novel dysregulated target molecules involved in locomotor function
Description	Thyroid hormone (TH) transporter MCT8 deficiency causes severe locomotor disabilities likely due to insufficient TH transport across brain barriers and, consequently, compromised neural TH action. As an established animal model for this disease Mct8/Oatp1c1 double knockout (DKO) mice exhibit strong central TH deprivation, locomotor impairments and similar histo-morphological features as seen in MCT8 patients. The pathways that cause these neuro-motor symptoms are poorly understood. Here, we performed proteome analysis of brain sections comprising cortical and striatal areas of 21-day-old WT and DKO mice. We detected over 2900 proteins by liquid chromatography mass spectrometry, 67 of which were significantly different between the genotypes. Comparison of the proteomic and published RNA-sequencing data showed a significant overlap between alterations in both datasets. In line with previous observations, DKO animals exhibited decreased myelin-associated protein expression and altered protein levels of well-established neuronal TH regulated targets. As one intriguing new candidate, we unraveled and confirmed reduced protein and mRNA expression of Pde10a, a striatal enzyme critically involved in dopamine receptor signaling, in DKO mice. As altered PDE10A activities are linked to dystonia, reduced basal ganglia PDE10A expression may represent a key pathogenic pathway underlying human MCT8 deficiency.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:25:00.474.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bente Siebels
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-28 06:05:20	ID requested
1	2023-10-27 05:13:22	announced
⏵ 2	2023-11-14 08:25:00	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: T4, Slc16a2, Allan-Herndon-Dudley Syndrome, Slco1c1, CNS, myelination, basal ganglia, Mct8, T3, Oatp1c1

Daniel Robert Engel
contact affiliation	University Duisburg-Essen, Institute for Experimental Immunology and Imaging, Dept. of Immunodynamics
contact email	danielrobert.engel@uni-due.de
lab head
Bente Siebels
contact affiliation	Section for Mass spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf
contact email	b.siebels@uke.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045769
     1. Label: PRIDE project
     2. Name: Proteome analysis of thyroid hormone transporter Mct8/Oatp1c1 deficient mice reveals novel dysregulated target molecules involved in locomotor function