# Mitogenic Activities in Neurofibromatosis

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $445,976

## Abstract

Individuals with neurofibromatosis type 1 (NF1) carry mutations in the NF1 tumor suppressor
gene and develop benign peripheral nerve sheath tumors (neurofibromas) that cause significant
morbidity, and mortality if they compress vital structures, and which can transform to malignant
peripheral nerve sheath tumors (MPNST). Neurofibromas contain normal nerve constituents:
axons, Schwann cells, fibroblasts, macrophages and mast cells, and aberrant Schwann cells
free of axons. Tumorigenesis results from complete loss of function at NF1, as neurofibroma
Schwann cells are characterized by biallelic mutations in NF1, with other cell types recruited
secondarily. We developed mouse model systems that are accurate mimics of neurofibroma
formation in NF1, and performed large scale gene expression array analyses to identify
candidate genes relevant to neurofibroma formation. Our robust Preliminary Data shows that a
chemokine receptor, Cxcr3, is crucial for neurofibroma formation. In this application, we
propose to use unique mouse models, neurofibroma Schwann cell precursors and Schwann
cells to define the chemokine pathways through which Nf1 loss in Schwann cells leads to the
presence of Cxcr3+ cells in neurofibroma (Aim 1) and to define CXCr3-expressing cells in
neurofibroma and test their function (Aim 2). Finally, we will define molecules that are
overexpressed in neurofibroma Schwann cells and are necessary for their survival (Aim 3).
Together these studies will identify cellular and molecular underpinnings of tumor formation in
the nervous system, and identify therapeutic targets for the treatment of NF1.

## Key facts

- **NIH application ID:** 10217260
- **Project number:** 5R01NS028840-30
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** NANCY RATNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $445,976
- **Award type:** 5
- **Project period:** 1990-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217260

## Citation

> US National Institutes of Health, RePORTER application 10217260, Mitogenic Activities in Neurofibromatosis (5R01NS028840-30). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217260. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*