# Generation of a plasma cell-specific inducible Cre transgenic mouse

> **NIH NIH R03** · UPSTATE MEDICAL UNIVERSITY · 2021 · $81,000

## Abstract

Project Summary/Abstract
 Plasma cells produce antibodies in response to infection or vaccination, but also play pathogenic roles
in autoimmunity and organ transplant. Despite the critical role of plasma cells in humoral immunity, there is
currently no transgenic mouse model that allows for conditional deletion of genes specifically in plasma cells.
This proposal aims to generate and validate a mouse model that expresses an inducible Cre specifically in
plasma cells. This goal will be achieved by using piggyBac transposase to insert a BAC cassette containing the
tamoxifen inducible CreERT2 gene upstream of the Tnfrsf17 locus. Tnfrsf17 encodes the protein B cell
maturation antigen (BCMA) and is expressed exclusively in plasma cells. Since BCMA is critical for plasma cell
survival and knock-in or CRISPR/Cas9 techniques can result in a null allele, BAC technology provides
advantageous alternative because it leaves endogenous gene expression intact. Aim 1 will set out to generate
the mouse model and Aim 2 will be dedicated to validating the specificity and efficiency of the model. To test
specificity to the plasma cell lineage, the BCMA-CreERT2 mouse will be crossed to the lineage-tracing mouse
R26R-EYFP. When these mice are treated with tamoxifen the plasma cells will activate Cre recombinase and
delete a loxP flanked stop codon upstream of Rosa26 driven EYFP, irreversibly labeling the plasma cells.
Since loxP sites at the Rosa26 locus are notoriously sensitive to Cre, we will also test the ability of the BCMA-
CreERT2 mouse to efficiently delete the Mcl-1 gene from Mcl-1fl/fl mice. Long-lived plasma cells require Mcl-1
for survival and therefore efficient deletion will result in the loss of the standing pool of long-lived plasma cells.
Upon completion of these aims, the BCMA-CreERT2 mouse will be a valuable tool for the analysis of long-lived
plasma cells leading to research that will advance the treatment of a variety of diseases.

## Key facts

- **NIH application ID:** 10110611
- **Project number:** 1R03AI156481-01
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Joel R Wilmore
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $81,000
- **Award type:** 1
- **Project period:** 2021-03-19 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110611

## Citation

> US National Institutes of Health, RePORTER application 10110611, Generation of a plasma cell-specific inducible Cre transgenic mouse (1R03AI156481-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10110611. Licensed CC0.

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