PUBLICATION
Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2
- Authors
- Desingu Rajan, A.R., Huang, Y., Stundl, J., Chu, K., Irodi, A., Yang, Z., Applegate, B.E., Bronner, M.E.
- ID
- ZDB-PUB-241018-13
- Date
- 2024
- Source
- Disease models & mechanisms 17(12): (Journal)
- Registered Authors
- Bronner-Fraser, Marianne
- Keywords
- Cancer, Inducible knockout, Meninges, Neurofibromatosis type 2, Schwann cells, Zebrafish
- MeSH Terms
-
- Animals, Genetically Modified
- Neurofibromin 2*/deficiency
- Neurofibromin 2*/genetics
- Neurofibromin 2*/metabolism
- Neurofibromatosis 2/genetics
- Neurofibromatosis 2/metabolism
- Neurofibromatosis 2/pathology
- Disease Models, Animal*
- Humans
- Animals
- Zebrafish*/embryology
- Zebrafish*/genetics
- Schwann Cells/metabolism
- Schwann Cells/pathology
- Zebrafish Proteins*/deficiency
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Cell Proliferation
- Larva/metabolism
- Gene Knockout Techniques*
- Neurofibromatoses/genetics
- Neurofibromatoses/metabolism
- Neurofibromatoses/pathology
- PubMed
- 39415595 Full text @ Dis. Model. Mech.
Citation
Desingu Rajan, A.R., Huang, Y., Stundl, J., Chu, K., Irodi, A., Yang, Z., Applegate, B.E., Bronner, M.E. (2024) Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2. Disease models & mechanisms. 17(12):.
Abstract
Neurofibromatosis Type 2 (NF-2) is a dominantly inherited genetic disorder that results from mutations in the tumor suppressor gene, neurofibromin 2 (NF2) gene. Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by an inducible genetic knockout of nf2a/b, the zebrafish homolog of human NF2. Analysis of nf2a and nf2b expression reveals ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displays lower expression levels. Induction of nf2a/b knockout at early stages increases the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggers the development of a spectrum of tumors, including vestibular Schwannomas, spinal Schwannomas, meningiomas, and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping