Related Experiment Video
Updated: Nov 3, 2025
06:55
Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions
Published on: June 7, 2020
3.1K
Characterization of PARP6 Function in Knockout Mice and Patients with Developmental Delay
Anke Vermehren-Schmaedick1,2, Jeffrey Y Huang3, Madison Levinson3
1Hospital & Specialty Medicine, VA Portland Health Care System, Portland, OR 97239, USA.
Cells
|June 2, 2021
Summary
Poly-ADP-ribose polymerase 6 (PARP6) is crucial for neuronal development and survival. Loss of PARP6 catalytic activity in mice and humans leads to neurodevelopmental disorders and perinatal death.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Poly-ADP-ribose polymerase 6 (PARP6) is a neuronally enriched enzyme.
- Previous studies suggest PARP6 regulates dendrite morphogenesis in vitro.
- The in vivo function of PARP6 in the nervous system remains largely unknown.
Purpose of the Study:
- To investigate the in vivo function of PARP6 during neurodevelopment.
- To characterize a novel Parp6 loss-of-function mouse model.
- To explore the role of PARP6 in human neurodevelopmental disorders.
Main Methods:
- Generation of a Parp6 loss-of-function mouse model using CRISPR-Cas9.
- Analysis of Parp6 truncated variants (Parp6TR) and mutations (C563R).
- BioID proximity labeling and proteomics in hippocampal neurons.
Main Results:
- Parp6 loss-of-function mice die perinatally, indicating essential catalytic activity for survival.
- PARP6 mutations are associated with human neurodevelopmental disorders like microcephaly and epilepsy.
- Loss of PARP6 catalytic activity impairs dendrite morphogenesis and identifies microtubule-binding proteins.
Conclusions:
- PARP6 catalytic activity is essential for postnatal survival in mice.
- PARP6 is a critical microtubule-regulatory gene.
- Disruption of PARP6 function has severe consequences for neuronal development and function in both mice and humans.
