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Updated: Jan 3, 2026
A Mouse Model of Fatigue Induced by Peripheral Irradiation
Published on: March 17, 2017
Effects of Brain Irradiation in Immune-Competent and Immune-Compromised Mouse Models
Mohammad Saki1, Kruttika Bhat1, Sirajbir S Sodhi1
1Departments of Radiation Oncology, David Geffen School of Medicine.
Abstract:
Patient-derived orthotopic xenografts (PDOXs) closely recapitulate primary human glioblastoma (GBM) tumors in terms of histology and genotype. Compared to other mouse strains, NOD-scid IL2Rgammanull (NSG) mice show excellent tumor take rates, which makes them an ideal host for PDOXs. However, NSG mice harbor a mutation in the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which renders them relatively radiosensitive. This has been a frequently voiced concern in studies involving ionizing radiation. In this study, we assessed brain toxicity in NSG mice compared to three other different mouse strains frequently used in radiation studies at radiation doses commonly used in experimental combination therapy studies. C3H/Sed/Kam, C57Bl/6, nude and NOD-scid IL2Rgammanull mice received a single dose of 4 Gy to the right brain hemispheres using an image-guided small animal irradiator. Brains were stained using H&E, luxol fast blue, and antibodies against IBA1 and GFAP one, two, four or six months postirradiation. Additional animals of all four strains were exposed to five daily fractions of 2 Gy (5 × 2 Gy), and tissue sections were stained 72 h later against gH2AX, NeuN, GFAP and IBA1. None of the mouse strains displayed radiation-induced toxicity at any of the time points tested. Radiation doses relevant for testing combination therapies can be safely applied to the brains of NSG mice without the occurrence of radiation-induced normal tissue toxicity.
Insights
NOD-scid IL2Rgammanull (NSG) mice are suitable for glioblastoma research using patient-derived orthotopic xenografts. Studies show these mice tolerate standard radiation doses without significant brain toxicity, supporting their use in combination therapy research.
Area of Science:
- Oncology
- Radiation Oncology
- Preclinical Research
Background:
- Patient-derived orthotopic xenografts (PDOXs) accurately model human glioblastoma (GBM).
- NOD-scid IL2Rgammanull (NSG) mice are preferred for PDOX models due to high tumor take rates.
- NSG mice possess a DNA-dependent protein kinase catalytic subunit (DNA-PKcs) mutation, raising concerns about radiosensitivity.
Purpose of the Study:
- To evaluate brain toxicity in NSG mice compared to other strains after irradiation.
- To determine if commonly used radiation doses for combination therapy studies are safe in NSG mice.
Main Methods:
- Four mouse strains (C3H/Sed/Kam, C57Bl/6, nude, and NSG) were irradiated.
- Mice received either a single 4 Gy dose or five daily 2 Gy fractions to the brain hemisphere.
- Brain tissues were analyzed histologically and immunohistochemically at various time points post-irradiation.
Main Results:
- No radiation-induced brain toxicity was observed in any of the tested mouse strains at any time point.
- Histological and molecular analyses did not reveal adverse effects from the applied radiation doses.
Conclusions:
- Radiation doses commonly used in experimental glioblastoma combination therapy studies can be safely administered to the brains of NSG mice.
- NSG mice can be used for preclinical radiation studies involving PDOX models without concerns of radiation-induced normal tissue toxicity.
