Neurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed 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 displayed lower expression levels. Induction of nf2a/b knockout at early stages increased the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggered 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.
- MeSH
- dánio pruhované * genetika embryologie MeSH
- geneticky modifikovaná zvířata MeSH
- genový knockout * MeSH
- larva metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- neurofibromatóza 2 genetika patologie metabolismus MeSH
- neurofibromatózy genetika patologie metabolismus MeSH
- neurofibromin 2 * genetika metabolismus nedostatek MeSH
- proliferace buněk MeSH
- proteiny dánia pruhovaného * genetika metabolismus nedostatek MeSH
- Schwannovy buňky metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
