# Generation and characterization of CD43-floxed mice for conditional ablation in hematopoietic cells and T cells in immunity against pulmonary fungal infections

> **NIH NIH R03** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2024 · $73,769

## Abstract

PROJECT SUMMARY
Small Grant Program R03 proposal aims to generate CD43-floxed mice using the CRISPR-Cas9 technology
and characterize the cell-specific antifungal functions of CD43 in hematopoietic and T cells using conditional
CD43 KO mice. The preclinical model systems have been invaluable, providing insights into the human
system, understanding the immune mechanisms, developing vaccines and immune therapeutics, and
facilitating novel discoveries relevant to human medicine. Fungal infections, in the face of a lack of vaccines,
cause significant mortality, rivaling TB and malaria, and instigated devastating complications during the
COVID-19 pandemic. Further, the continuous rise in the immune-compromised or suppressed population by
both nosocomial and non-nosocomial factors, as well as the expansion of fungal habitat due to climate change,
has heightened the risk of fungal infections and posed a horde of public health challenges. A major limitation in
the immune control of respiratory fungal infections is a lack of knowledge of protective host defense
mechanisms, both innate and adaptive. Sialophorin (CD43) is implicated in viral, bacterial, parasitic, and fungal
infections. CD43 research has shed light on its costimulatory/inhibitory, adhesive/anti-adhesive cell property,
inhibiting or promoting apoptosis, receptor microbes/microbial product, binding several ligands, and in the
aggressiveness of several lymphoid, myeloid, and epithelial cancer cells. The functionality and expression in
several cell types with often counterintuitive phenotypes in the functions of CD43 have clouded our
understanding and myopic views of its cell-specific functions. Regrettably, CD43-floxed mice are unavailable
and are necessary to address much confounding research, including ours. Our preliminary data showed that
CD43 (using global KO) is essential for immunity in a mouse model of pulmonary fungal infections, but we
unexpectedly found its role in non-hematopoietic cells, contrary to our understanding its role in hematopoietic
cells. In line with this, differing from the mouse model of viral infection, we found an essential role of CD43
(using global CD43 KO) for CD8+ T cell responses to fungal vaccinations and vaccine immunity. Therefore, we
propose generating a CD43-floxed mouse to address the cell-specific role of CD43 in immunity against fungal
infections by developing conditional CD43 KO. Our overarching hypothesis is that CD43 is integral in
hematopoietic and non-hematopoietic cell responses in immunity against respiratory fungal infection. We aim
to (1) generate CD43-floxed mice using the CRISPR-Cas9 technology to develop conditional KO mice and (2)
Characterize CD43-floxed mice by generating conditional KO mice for immunity against fungal pneumonia and
responses to the fungal vaccine. The outcomes of our projects will help advance our understanding of the cell-
specific functions of CD43 during fungal infection and open universal applications in biomedical r...

## Key facts

- **NIH application ID:** 10870436
- **Project number:** 1R03AI182772-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Somashekarappa Gowda Nanjappa
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,769
- **Award type:** 1
- **Project period:** 2024-06-17 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870436

## Citation

> US National Institutes of Health, RePORTER application 10870436, Generation and characterization of CD43-floxed mice for conditional ablation in hematopoietic cells and T cells in immunity against pulmonary fungal infections (1R03AI182772-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10870436. Licensed CC0.

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