PXD025386

PXD025386 is an original dataset announced via ProteomeXchange.

Title	Characterization of PARP-6 function in knock out mice and patients with developmental delay
Description	PARP-6, a member of a family of enzymes (17 in humans) known as poly-ADP- ribose polymerases (PARPs), is a neuronally enriched PARP. While previous studies from our group show that PARP-6 is a regulator of dendrite morphogenesis in hippocampal neurons, its function in the nervous system in vivo is poorly understood. Here, we describe the generation of a PARP-6 loss-of-function mouse model for examining the function of PARP-6 during neurodevelopment in vivo. Using CRISPR-Cas9 mutagenesis, we generated a mouse line that expresses a PARP-6 truncated variant (PARP-6TR) in place of PARP-6WT. Unlike PARP-6WT, PARP-6TR is devoid of catalytic activity. Homozygous PARP-6TR do not exhibit obvious neuromorphological defects during development, but nevertheless die perinatally. This suggests that PARP-6 catalytic activity is important for postnatal survival. We also report PARP-6 mutations in six patients with several neurodevelopmental disorders, including microencephaly, intellectual disabilities, and epilepsy. The most severe mutation in PARP-6 (C563R) results in the loss of catalytic activity. Expression of the PARP-6C563R mutant in hippocampal neurons decreases dendrite morphogeneis. Taken together, these results suggest that PARP-6 is an essential gene in mice, and the loss of PARP-6 catalytic activity has detrimental effects on neuronal function in humans.
HostingRepository	PRIDE
AnnounceDate	2021-07-21
AnnouncementXML	Submission_2021-07-21_15:02:53.661.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-14 01:57:11	ID requested
⏵ 1	2021-07-21 15:02:54	announced

Vermehren-Schmaedick A, Huang JY, Levinson M, Pomaville MB, Reed S, Bellus GA, Gilbert F, Keren B, Heron D, Haye D, Janello C, Makowski C, Danhauser K, Fedorov LM, Haack TB, Wright KM, Cohen MS, Characterization of PARP6 Function in Knockout Mice and Patients with Developmental Delay. Cells, 10(6):(2021) [pubmed]

submitter keyword: ADP-ribosylation, MARylation, PARP-6

nervous system, dendritic branching, BioID, Orbitrap Fusion, Spectral Counts

Michael S. Cohen
contact affiliation	Department of Physiology and Pharmacology Oregon Health & Science University Portland, Oregon 97210, USA
contact email	cohenmic@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
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/2021/07/PXD025386

PRIDE project URI

• PRIDE
  1. PXD025386
     1. Label: PRIDE project
     2. Name: Characterization of PARP-6 function in knock out mice and patients with developmental delay