# Studies to understand how mutations in the IKZF1 gene can contribute to development of autoimmune disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $19,998

## Abstract

ABSTRACT
Autoimmune diseases affect millions of Americans and are chronic and often disabling illnesses with no cures.
Current treatments help to prevent the symptoms of autoimmune disease, but there is a need for greater
understanding of the underlying mechanisms of disease in order to facilitate improved treatments, and perhaps
one day – a cure. Current knowledge indicates that autoimmune disease arise due to a combination of genetic
predispositions and environmental factors, but the etiology is not fully understood. We are studying one of the
genetic factors that are implicated in human autoimmunity through both genome-wide association studies
(GWAS) and recently identified patients with mutations in this gene. Using a newly established strain of mutant
mice, we found a profound defect in immune tolerance, with high levels of autoreactive antibodies in the serum
of very young mice. Antibodies are produced by B cells, and the presence of autoreactive antibodies indicates
that this gene is necessary to control how B cells respond to antigen and to ensure tolerance to self. We propose
to employ our mutant mice as a new model of autoimmunity to investigate the molecular mechanisms underlying
the break of tolerance. We have preliminary data demonstrating lung infiltrates in this mouse models, and
propose for the Fellowship candidate to investigate the cellular composition and subtype identity of the infiltrating
cells. Furthermore, we have indications that gene isoform expression is important in the proper regulation of
immune tolerance, and propose that the Fellowship candidate investigates the gene isoform expression across
different stages of B-cell development. The work will be supplementing the work in the parental grant, and the
candidate will be trained by current members of the laboratory research group.

## Key facts

- **NIH application ID:** 9971329
- **Project number:** 3R01AI127709-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Seth E Frietze
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $19,998
- **Award type:** 3
- **Project period:** 2018-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971329

## Citation

> US National Institutes of Health, RePORTER application 9971329, Studies to understand how mutations in the IKZF1 gene can contribute to development of autoimmune disease (3R01AI127709-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971329. Licensed CC0.

---

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