# Creation and Characterization of Lineage-Restricted Stat5B KO Mice

> **NIH NIH R03** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $74,954

## Abstract

Project Summary
Signal transducers and activators of transcription (Stats) are transcription factors with critical
roles in the immune and endocrine systems. While there is considerable knowledge of Stat-
mediated gene control, we know far less about lineage-restricted Stat functions. Understanding
cell-specific actions is necessary for progress in diseases impacted by Stat dysfunction –
including cancer, infertility, metabolic disorders, immunodeficiency, and chronic inflammation.
We have evidence that Stat5B is pivotal for mast cell function. Like several other Stat proteins,
Stat5B forms dimers and tetramers. We find that Stat5B dimers and tetramers have some
similar and some opposing functions. Dimers and tetramers promote cytokine secretion. But
while Stat5B dimers promote mast cell histamine production and cell migration, tetramers
appear to inhibit both functions. These data are consistent in vitro and in a model of systemic
anaphylaxis. Therefore, our hypothesis is that Stat5B dimers and tetramers have distinct effects
on mast cell function, with tetramers often limiting the effects of dimers. Understanding this
fundamental biology has considerable translational potential. Therefore, we propose creating
several strains of mice that allow lineage-specific deletion of Stat5B or selective expression of a
Stat5B mutant that can form protein dimers but not tetramers. These mice will make possible
detailed studies of Stat5B, allowing us to understand how this protein contributes to the function
of specific cell types.

## Key facts

- **NIH application ID:** 10870605
- **Project number:** 1R03AI182614-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** John J Ryan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,954
- **Award type:** 1
- **Project period:** 2024-06-14 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870605

## Citation

> US National Institutes of Health, RePORTER application 10870605, Creation and Characterization of Lineage-Restricted Stat5B KO Mice (1R03AI182614-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10870605. Licensed CC0.

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