| RRC ID |
87472
|
| Author |
Ujibe K, Kashima M, Kataoka M, Shimada R, Okamoto M, Kobayashi I, Wada S, Matsuda H, Sakamoto A, Hirata H.
|
| Title |
Deficiency of Werner RecQ-type DNA helicase causes premature malnutrition in zebrafish.
|
| Journal |
iScience
|
| 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.
|
| Volume |
29(3)
|
| Pages |
114760
|
| Published |
2026-3-20
|
| DOI |
10.1016/j.isci.2026.114760
|
| PII |
S2589-0042(26)00135-5
|
| PMID |
41732282
|
| PMC |
PMC12924724
|
| Resource |
| Zebrafish |
wrn agu26 |
