PUBLICATION
Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior
- Authors
- Biran, J., Gliksberg, M., Shirat, I., Swaminathan, A., Levitas-Djerbi, T., Appelbaum, L., Levkowitz, G.
- ID
- ZDB-PUB-200615-3
- Date
- 2020
- Source
- Scientific Reports 10: 9559 (Journal)
- Registered Authors
- Appelbaum, Lior, Biran, Jacob, Gliksberg, Michael, Levitas-Djerbi, Tali, Levkowitz, Gil, Shirat, Ido, Swaminathan, Amrutha
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 32533011 Full text @ Sci. Rep.
Citation
Biran, J., Gliksberg, M., Shirat, I., Swaminathan, A., Levitas-Djerbi, T., Appelbaum, L., Levkowitz, G. (2020) Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior. Scientific Reports. 10:9559.
Abstract
The pituitary adenylate cyclase-activating polypeptide receptor (PAC1, also known as ADCYAP1R1) is associated with post-traumatic stress disorder and modulation of stress response in general. Alternative splicing of PAC1 results in multiple gene products, which differ in their mode of signalling and tissue distribution. However, the roles of distinct splice variants in the regulation of stress behavior is poorly understood. Alternative splicing of a short exon, which is known as the "hop cassette", occurs during brain development and in response to stressful challenges. To examine the function of this variant, we generated a splice-specific zebrafish mutant lacking the hop cassette, which we designated 'hopless'. We show that hopless mutant larvae display increased anxiety-like behavior, including reduced dark exploration and impaired habituation to dark exposure. Conversely, adult hopless mutants displayed superior ability to rebound from an acute stressor, as they exhibited reduced anxiety-like responses to an ensuing novelty stress. We propose that the developmental loss of a specific PAC1 splice variant mimics prolonged mild stress exposure, which in the long term, predisposes the organism's stress response towards a resilient phenotype. Our study presents a unique genetic model demonstrating how early-life state of anxiety paradoxically correlates with reduced stress susceptibility in adulthood.
Errata / Notes
This article is corrected by ZDB-PUB-220906-211 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping