PUBLICATION
Zebrafish Carrying pycr1 Gene Deficiency Display Aging and Multiple Behavioral Abnormalities
- Authors
- Liang, S.T., Audira, G., Juniardi, S., Chen, J.R., Lai, Y.H., Du, Z.C., Lin, D.S., Hsiao, C.D.
- ID
- ZDB-PUB-190517-1
- Date
- 2019
- Source
- Cells 8(5): (Journal)
- Registered Authors
- Hsiao, Chung-Der
- Keywords
- PYCR1, TALEN, aging, behavioral alteration, disease model, zebrafish
- MeSH Terms
-
- Aging/genetics*
- Aging/metabolism
- Animals
- Behavioral Symptoms/genetics*
- Disease Models, Animal*
- Energy Metabolism
- Extracellular Matrix/metabolism
- Gene Knockout Techniques
- Locomotion
- Loss of Function Mutation
- Mitochondria/metabolism
- Models, Animal*
- Progeria/genetics*
- Proline/metabolism
- Pyrroline Carboxylate Reductases/genetics*
- Pyrroline Carboxylate Reductases/physiology
- Superoxide Dismutase/metabolism
- Zebrafish/genetics*
- PubMed
- 31091804 Full text @ Cells
Citation
Liang, S.T., Audira, G., Juniardi, S., Chen, J.R., Lai, Y.H., Du, Z.C., Lin, D.S., Hsiao, C.D. (2019) Zebrafish Carrying pycr1 Gene Deficiency Display Aging and Multiple Behavioral Abnormalities. Cells. 8(5):.
Abstract
Aging is a natural process that internal gene control and external stimuli mediate. Clinical data pointed out that homozygotic or heterozygotic mutation in the pyrroline-5-carboxylate reductase 1 (PYCR1) gene in humans caused cutis laxa (ARCL) disease, with progeroid appearance, lax and wrinkled skin, joint laxity, osteopenia, and mental retardation phenotypes. In this study, we aimed to generate pycr1 knockout (KO) zebrafish and carried out biochemical characterizations and behavior analyses. Marked apoptosis and senescence were detected in pycr1 KO zebrafish, which started from embryos/larvae stage. Biochemical assays showed that adult pycr1 KO fish have significantly reduced proline and extracellular matrix contents, lowered energy, and diminished superoxide dismutase (SOD) and telomerase activity when compared to the wild type fish, which suggested the pycr1 KO fish may have dysfunction in mitochondria. The pycr1 KO fish were viable; however, displayed progeria-like phenotype from the 4 months old and reach 50% mortality around six months old. In adult stage, we found that pycr1 KO fish showed reduced locomotion activity, aggression, predator avoidance, social interaction interest, as well as dysregulated color preference and circadian rhythm. In summary, we have identified multiple behavioral alterations in a novel fish model for aging with pycr1 gene loss-of-function by behavioral tests. This animal model may not only provide a unique vertebrate model to screen potential anti-aging drugs in the future, but also be an excellent in vivo model towards a better understanding of the corresponding behavioral alterations that accompany aging.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping