Protocol to establish a genetically engineered mouse model of IDH1-mutant astrocytoma

Diana D Shi; Joyce H Lee; Adam C Wang; Januka Khanal; Wenhua Gao; William G Kaelin Jr; Samuel K McBrayer

doi:10.1016/j.xpro.2023.102281

Protocol to establish a genetically engineered mouse model of IDH1-mutant astrocytoma

STAR Protoc. 2023 May 6;4(2):102281. doi: 10.1016/j.xpro.2023.102281. Online ahead of print.

Authors

Diana D Shi¹, Joyce H Lee², Adam C Wang², Januka Khanal², Wenhua Gao², William G Kaelin Jr³, Samuel K McBrayer⁴

Affiliations

¹ Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA 02215, USA; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: dshi1@partners.org.
² Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
⁴ Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. Electronic address: samuel.mcbrayer@utsouthwestern.edu.

Abstract

Lower-grade gliomas exhibit a high prevalence of isocitrate dehydrogenase 1 (IDH1) mutations, but faithful models for studying these tumors are lacking. Here, we present a protocol to establish a genetically engineered mouse (GEM) model of grade 3 astrocytoma driven by the Idh1^R132H oncogene. We describe steps for breeding compound transgenic mice and intracranially delivering adeno-associated virus particles, followed by post-surgical surveillance via magnetic resonance imaging. This protocol enables the generation and use of a GEM to study lower-grade IDH-mutant gliomas. For complete details on the use and execution of this protocol, please refer to Shi et al. (2022).¹.

Keywords: Cancer; Model Organisms; Neuroscience.