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Updated: Feb 14, 2026
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Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
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STAT3R152W Mutation Model Reveals Temporal Changes in Hematopoietic Populations.
Jakub Jankowski1, Jichun Chen2, Sung-Gwon Lee1
1Section of Genetics and Physiology, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, MD 20892, USA.
International Journal of Molecular Sciences
|February 13, 2026
Summary
The STAT3 R152W variant causes immune dysregulation but acts as a cofactor in autoimmunity development. This mouse model reveals complex changes in innate and adaptive immunity over time.
Area of Science:
- Immunology
- Genetics
- Hematology
Background:
- STAT3 variants present challenges in clinical diagnostics and outcome prediction.
- The STAT3 R152W variant is linked to autoimmune disorders, but its direct role is unclear due to complex genetic and environmental factors.
Purpose of the Study:
- To develop and characterize a mouse model for the STAT3 R152W variant.
- To investigate the impact of the STAT3 R152W variant on hematopoietic populations and immune function throughout adulthood.
Main Methods:
- Generation of a STAT3 R152W variant mouse model.
- Analysis of hematopoietic populations and immune cell profiles in adult mice.
- Longitudinal observation of immune changes and potential autoimmune phenotypes.
Main Results:
- STAT3 R152W mice exhibited profound innate and adaptive immune changes, including an increased splenic Th17 component, suggesting gain-of-function.
- Mice did not develop overt autoimmune symptoms but showed susceptibility to anemia (lowered hemoglobin and hematocrit) and increased thrombocyte counts.
- Observed temporal dynamics and sex-based differences in immune dysregulation.
Conclusions:
- The STAT3 R152W variant is a significant cause of immune dysregulation.
- STAT3 R152W acts as a cofactor, not a sole cause, in the development of autoimmunity.
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