PUBLICATION
Loss of atm in Zebrafish as a Model of Ataxia-Telangiectasia Syndrome
- Authors
- Chen, K., Wang, P., Chen, J., Ying, Y., Chen, Y., Gilson, E., Lu, Y., Ye, J.
- ID
- ZDB-PUB-220226-4
- Date
- 2022
- Source
- Biomedicines 10(2): (Journal)
- Registered Authors
- Chen, Yi
- Keywords
- ATM, immune deficiency, regeneration, tumorigenesis, zebrafish
- MeSH Terms
- none
- PubMed
- 35203601 Full text @ Biomedicines
Citation
Chen, K., Wang, P., Chen, J., Ying, Y., Chen, Y., Gilson, E., Lu, Y., Ye, J. (2022) Loss of atm in Zebrafish as a Model of Ataxia-Telangiectasia Syndrome. Biomedicines. 10(2):.
Abstract
Ataxia-telangiectasia mutated (ATM) is a key DNA damage signaling kinase that is mutated in humans with ataxia-telangiectasia (A-T) syndrome. This syndrome is characterized by neurodegeneration, immune abnormality, cancer predisposition, and premature aging. To better understand the function of ATM in vivo, we engineered a viable zebrafish model with a mutated atm gene. Zebrafish atm loss-of-function mutants show characteristic features of A-T-like motor disturbance, including coordination disorders, immunodeficiency, and tumorigenesis. The immunological disorder of atm homozygote fish is linked to the developmental blockade of hematopoiesis, which occurs at the adulthood stage and results in a decrease in infection defense but, with little effect on wound healing. Malignant neoplasms found in atm mutant fish were mainly nerve sheath tumors and myeloid leukemia, which rarely occur in A-T patients or Atm-/- mice. These results underscore the importance of atm during immune cell development. This zebrafish A-T model opens up a pathway to an improved understanding of the molecular basis of tumorigenesis in A-T and the cellular role of atm.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping