# Cadherin-11-cre deleter mouse

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $76,298

## Abstract

ABSTRACT
The objective of this grant application is to validate a novel mouse model enabling gene deletion in
arthritogenic fibroblast-like synoviocytes (FLS). FLS are local joint-lining non hematopoietic cells that
significantly contribute to joint and bone damage in active rheumatoid arthritis. This cell type is considered as a
promising target for novel therapies to enhance control of disease activity and/or spare immunosuppression in
patients with rheumatoid arthritis. However, the lack of a deleter mouse strain able to induce gene deletion
specifically in FLS and their key subpopulations has been a serious limitation to both our understanding of the
mechanism of action of this cell type in RA, and to the validation of novel targets for FLS-directed therapies.
To begin addressing this bottleneck in the field, we have generated a novel deleter mouse strain that for the
first time enables gene deletions specifically driven by the promoter of cadherin-11, a molecule that marks an
aggressive population of FLS both in arthritic mice and humans with rheumatoid arthritis. In Aim 1 we will
provide evidence that our new cre deleter strain is expressed selectively in FLS and throughout the course of
experimental arthritis. In Aim 2 we will provide proof of principle evidence that cre expression in FLS does not
influence severity of disease and that the new strain is able to drive FLS-specific deletion of a test gene
believed to operate in arthritis via an action on FLS.
Our goal is to generate an important shared resource for everybody working in the FLS field. Thus, if the
studies funded by this grant succeed, we are firmly committed to depositing the model at JAX even before
publication, as soon as sufficient data are collected to support use of such a needed resource by the whole RA
research community.

## Key facts

- **NIH application ID:** 10150385
- **Project number:** 1R21AR078677-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Nunzio Bottini
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $76,298
- **Award type:** 1
- **Project period:** 2021-09-24 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150385

## Citation

> US National Institutes of Health, RePORTER application 10150385, Cadherin-11-cre deleter mouse (1R21AR078677-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10150385. Licensed CC0.

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