PXD003442

PXD003442 is an original dataset announced via ProteomeXchange.

Title	Integrated genomics and proteomics to define huntingtin CAG length-dependent molecular networks in HD mouse brains
Description	To gain insight into how mutant Huntingtin (mHTT) CAG repeat length may modify Huntington’s disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat length. We find repeat length dependent transcriptional signatures are prominent in the striatum, less so in cortex, and minimal in the liver. Co-expression network analyses reveal 13 striatal and 5 cortical modules that are highly correlated with CAG length and age, and that are preserved in HD models and some in the patients. Top striatal modules implicate mHTT CAG length and age in graded impairment of striatal medium spiny neuron identity gene expression and in dysregulation of cAMP signaling, cell death, and protocadherin genes. Importantly, we used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at both RNA and protein levels and validated 21 striatal module genes as modifiers of mHtt toxicities in vivo.
HostingRepository	PRIDE
AnnounceDate	2016-02-16
AnnouncementXML	Submission_2016-02-25_04:57:19.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christoph Schaab
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-01-11 03:12:53	ID requested
1	2016-02-16 10:29:56	announced
⏵ 2	2016-02-25 04:57:21	announced	Updated publication reference for PubMed record(s): 26900923.

Langfelder P, Cantle JP, Chatzopoulou D, Wang N, Gao F, Al-Ramahi I, Lu XH, Ramos EM, El-Zein K, Zhao Y, Deverasetty S, Tebbe A, Schaab C, Lavery DJ, Howland D, Kwak S, Botas J, Aaronson JS, Rosinski J, Coppola G, Horvath S, Yang XW, Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice. Nat Neurosci, 19(4):623-33(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Huntington disease, mouse brain, striatum, label-free, proteomics

Christoph Schaab
contact affiliation	Evotec (Munchen) GmbH, Am Klopferspitz 19a, 82152 Martinsried, Germany
contact email	christoph.schaab@evotec.com
lab head
Christoph Schaab
contact affiliation	Evotec
contact email	christoph.schaab@evotec.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/02/PXD003442

PRIDE project URI

• PRIDE
  1. PXD003442
     1. Label: PRIDE project
     2. Name: Integrated genomics and proteomics to define huntingtin CAG length-dependent molecular networks in HD mouse brains