PUBLICATION
A simple and scalable zebrafish model of Sonic hedgehog medulloblastoma
- Authors
- Casey, M.J., Chan, P.P., Li, Q., Zu, J.F., Jette, C.A., Kohler, M., Myers, B.R., Stewart, R.A.
- ID
- ZDB-PUB-240731-2
- Date
- 2024
- Source
- Cell Reports 43: 114559114559 (Journal)
- Registered Authors
- Jette, Cicely A., Stewart, Rodney A.
- Keywords
- CP: Cancer, CRISPR, GRK2, GRK3, PTCH1, SHH, TP53, cerebellum, medulloblastoma, pediatric brain tumors, zebrafish
- Datasets
- GEO:GSE242897
- MeSH Terms
-
- Animals
- CRISPR-Cas Systems/genetics
- Cerebellar Neoplasms/genetics
- Cerebellar Neoplasms/metabolism
- Cerebellar Neoplasms/pathology
- Disease Models, Animal*
- Hedgehog Proteins*/genetics
- Hedgehog Proteins*/metabolism
- Humans
- Medulloblastoma*/genetics
- Medulloblastoma*/metabolism
- Medulloblastoma*/pathology
- Patched-1 Receptor*/genetics
- Patched-1 Receptor*/metabolism
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Zebrafish*
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 39078737 Full text @ Cell Rep.
Citation
Casey, M.J., Chan, P.P., Li, Q., Zu, J.F., Jette, C.A., Kohler, M., Myers, B.R., Stewart, R.A. (2024) A simple and scalable zebrafish model of Sonic hedgehog medulloblastoma. Cell Reports. 43:114559114559.
Abstract
Medulloblastoma (MB) is the most common malignant brain tumor in children and is stratified into three major subgroups. The Sonic hedgehog (SHH) subgroup represents ∼30% of all MB cases and has significant survival disparity depending upon TP53 status. Here, we describe a zebrafish model of SHH MB using CRISPR to create mutant ptch1, the primary genetic driver of human SHH MB. In these animals, tumors rapidly arise in the cerebellum and resemble human SHH MB by histology and comparative onco-genomics. Similar to human patients, MB tumors with loss of both ptch1 and tp53 have aggressive tumor histology and significantly worse survival outcomes. The simplicity and scalability of the ptch1-crispant MB model makes it highly amenable to CRISPR-based genome-editing screens to identify genes required for SHH MB tumor formation in vivo, and here we identify the gene encoding Grk3 kinase as one such target.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping