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Updated: May 19, 2026
Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
Published on: October 16, 2017
Nras overexpression results in granulocytosis, T-cell expansion and early lethality in mice
Louise Berkhoudt Lassen1, Borja Ballarín-González, Alexander Schmitz
1Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Abstract:
NRAS is a proto-oncogene involved in numerous myeloid malignancies. Here, we report on a mouse line bearing a single retroviral long terminal repeat inserted into Nras. This genetic modification resulted in an increased level of wild type Nras mRNA giving the possibility of studying the function and activation of wild type NRAS. Flow cytometry was used to show a variable but significant increase of immature myeloid cells in spleen and thymus, and of T-cells in the spleen. At an age of one week, homozygous mice began to retard compared to their wild type and heterozygous littermates. Two weeks after birth, animals started to progressively lose weight and die before weaning. Heterozygous mice showed a moderate increase of T-cells and granulocytes but survived to adulthood and were fertile. In homozygous and heterozygous mice Gfi1 and Gcsf mRNA levels were upregulated, possibly explaining the increment in immature myeloid cells detected in these mice. The short latency period indicates that Nras overexpression alone is sufficient to cause dose-dependent granulocytosis and T-cell expansion.
Insights
Overexpressing the NRAS proto-oncogene in mice causes severe developmental defects and lethality in homozygous individuals. Heterozygous mice exhibit moderate increases in T-cells and granulocytes, highlighting NRAS
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- NRAS is a proto-oncogene implicated in various myeloid malignancies.
- Understanding NRAS function is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the functional consequences of wild-type NRAS overexpression in a mouse model.
- To analyze the impact of NRAS dysregulation on myeloid cell development and immune cell populations.
Main Methods:
- Generation of a novel mouse line with a retroviral long terminal repeat insertion in the Nras gene.
- Utilized flow cytometry to assess cell populations in spleen and thymus.
- Quantified mRNA levels of Gfi1 and Gcsf.
Main Results:
- Homozygous mice exhibited growth retardation, weight loss, and mortality before weaning.
- Significant increases in immature myeloid cells and T-cells were observed in homozygous mice.
- Heterozygous mice displayed moderate increases in T-cells and granulocytes but survived to adulthood.
- Upregulation of Gfi1 and Gcsf mRNA was noted in both homozygous and heterozygous mice.
Conclusions:
- NRAS overexpression is sufficient to induce dose-dependent granulocytosis and T-cell expansion.
- NRAS dysregulation plays a critical role in myeloid malignancies and immune system development.
- This mouse model provides a valuable tool for studying wild-type NRAS function and activation.
