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Updated: Jun 10, 2026
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
The stromal gene encoding the CD274 antigen as a genetic modifier controlling survival of mice with
J Santos1, L González-Sánchez, M Villa-Morales
1Departamento de Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas-Universidad Autínoma de Madrid, Madrid, Spain.
Abstract:
Using an inter-specific subcongenic strain, Nested Recombinant Haplotype 3 (NRH3), generated between two mouse strains showing extreme differences in γ-radiation-induced thymic lymphoma susceptibility (SEG/Pas and C57BL/6J), we have identified a critical region on chromosome 19 that regulates survival of mice suffering from T-cell lymphoblastic lymphomas. Mapped on this region, the gene encoding the Cd274 ligand is able to trigger an inhibitory effect that modulates T-cell receptor (TCR) signalling and affects thymocyte maturation. Interestingly, this gene shows differential expression between thymic stromal cells from both strains in early response to a single sublethal γ-ray dose, but is inhibited in T-cell lymphoblastic lymphomas. Furthermore, we have identified several polymorphisms in the complementary DNA sequence of this gene that affect the affinity for its Cd279 receptor and are able to induce a differential rate of thymocyte apoptosis. Taken together, our data are consistent with Cd274 acting as a genetic modifier that influences the survival of γ-radiation-induced T-cell lymphoma-bearing mice. The data similarly support the idea of a co-evolution of tumour cells and associated stromal cells to generate a favourable microenvironment for T-cell lymphoma growth.
Insights
A critical gene region on mouse chromosome 19 influences survival in radiation-induced T-cell lymphomas. The Cd274 gene modulates T-cell receptor signaling and apoptosis, impacting lymphoma growth.
Area of Science:
- Immunology
- Cancer Biology
- Radiation Oncology
Background:
- Mouse strains SEG/Pas and C57BL/6J exhibit significant differences in susceptibility to gamma-radiation-induced thymic lymphoma.
- Understanding genetic factors influencing lymphoma development and survival is crucial for therapeutic strategies.
Purpose of the Study:
- To identify genetic regions regulating survival in mice with T-cell lymphoblastic lymphomas induced by gamma radiation.
- To investigate the role of the Cd274 gene and its polymorphisms in lymphoma development and progression.
Main Methods:
- Utilized an inter-specific subcongenic mouse strain, Nested Recombinant Haplotype 3 (NRH3).
- Mapped a critical genetic region on chromosome 19 associated with lymphoma survival.
- Analyzed Cd274 gene expression, polymorphisms, and its interaction with the Cd279 receptor.
Main Results:
- Identified a critical region on chromosome 19 regulating survival in T-cell lymphoblastic lymphomas.
- The Cd274 ligand gene inhibits T-cell receptor signaling, affecting thymocyte maturation and survival.
- Cd274 polymorphisms impact receptor affinity and thymocyte apoptosis rates, influencing lymphoma progression.
Conclusions:
- Cd274 acts as a genetic modifier influencing survival in gamma-radiation-induced T-cell lymphoma-bearing mice.
- Tumor and stromal cells co-evolve to create a microenvironment supporting T-cell lymphoma growth.
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