PUBLICATION
Deficiency of Werner RecQ-type DNA helicase causes premature malnutrition in zebrafish
- Authors
- Ujibe, K., Kashima, M., Kataoka, M., Shimada, R., Okamoto, M., Kobayashi, I., Wada, S., Matsuda, H., Sakamoto, A., Hirata, H.
- ID
- ZDB-PUB-260224-7
- Date
- 2026
- Source
- iScience 29: 114760114760 (Journal)
- Registered Authors
- Hirata, Hiromi, Kobayashi, Isao, Matsuda, Hiroki
- Keywords
- Developmental biology, Pathophysiology
- Datasets
- GEO:GSE276188
- MeSH Terms
- none
- PubMed
- 41732282 Full text @ iScience
Citation
Ujibe, K., Kashima, M., Kataoka, M., Shimada, R., Okamoto, M., Kobayashi, I., Wada, S., Matsuda, H., Sakamoto, A., Hirata, H. (2026) Deficiency of Werner RecQ-type DNA helicase causes premature malnutrition in zebrafish. iScience. 29:114760114760.
Abstract
Werner syndrome is a genetic progeria characterized by premature aging symptoms, but its early-onset pathology remains unclear. We generated wrn truncation mutant (wrn-/-) zebrafish using CRISPR/Cas9 and identified two premature mortality phases: 7-21 and 60-90 days post-fertilization (dpf). Time-course transcriptomics revealed two wrn-/- subgroups. One showed the reduced expression of intestinal and pancreatic exocrine genes at 7-9 dpf, while the other maintained normal expression initially but eventually showed reduced pancreatic exocrine genes by 21-35 dpf. The prematurely dying wrn-/- larvae exhibited intestinal villi and pancreatic defects, along with DNA damage, cell-cycle arrest, and apoptosis. They also had lower glycogen, glucose, and fat levels compared to wild-type and late-dying wrn-/- larvae, suggesting malnutrition. Notably, excess feeding partially improved their survival. These findings reveal early pathological features in the zebrafish model of Werner syndrome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping