Proteomics

Dataset Information

0

Characterization of PARP-6 function in knock out mice and patients with developmental delay


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Neuron

SUBMITTER: Phillip Wilmarth  

LAB HEAD: Michael S. Cohen

PROVIDER: PXD025386 | Pride | 2021-07-21

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
BP6_P2A_GFP_sprot_2016.06_rat_both.fasta Fasta
COH_BP6_1.raw Raw
COH_BP6_1_filtered.ms2 Other
COH_BP6_1_filtered.sqt Other
COH_BP6_1_filtered.txt Txt
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Publications


PARP6, 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 Parp6 is a regulator of dendrite morphogenesis in rat hippocampal neurons, its function in the nervous system in vivo is poorly understood. Here, we describe the generation of a <i>Parp6</i> loss-of-function mouse model for examining the function of Parp6 during neurodevelopment in vivo. Using CRISPR-Cas9 mutagenesis, w  ...[more]

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