# MECHANISMS OF AUTOIMMUNITY

> **NIH NIH R01** · JACKSON LABORATORY · 1989 · $143,999

## Abstract

This project will continue to focus on the cellular and genetic
mechanisms leading to autoimmunity in two classes of murine
models based on primary single gene mutations.  One class of
model is represented by the viable motheaten (me   ) mutation,
and seems to result from the aberrant expansion and lymphokine-
mediated autostimulation of a normally minor population of B
cells marked by the Ly-1 surface antigen.  In the second class of
models, which includes the lymphoproliferation (1pr) and
generalized lymphoproliferative disease (gld) mutations, B cell
hyperactivity appears secondary to T cell hyperplasia.  The
following two specific aims will be addressed:

1.  What cellular interactions, including those with other cells and
with soluble molecules such as lymphokines, are involved in the
development of autoimmunity?  This question will be approached
by studying cell and organ chimeras between genetically marked
and thus distinguishable normal and autoimmune donors, and by
creating mice bearing both a primary autoimmunity-inducing
mutation and other genes leading to the loss of specific
immunological cells or reactivities.

2.  What other genes influence the pattern or severity of
autoimmunity caused by the primary autoimmunity-inducing
mutations?  Mice homozygous for one of the primary
autoimmunity genes and congenic for various MHC, Ig, or T cell
receptor alleles, or with the primary genes on different genetic
backgrounds (via congenic lines) or combinations of backgrounds
(via RI strains), will be used to address this issue.

The parameters of autoimmunity to be assayed in these mice
include:  spontaneous antibody secretion (by polyclonal and
specific ELISA assays), cell phenotype (by immunofluorescent
staining and FACS analysis), lymphokines production (by in vitro
cellular assays and analysis of lymphokine mRNA levels), and
clinical course and immunopathology).  These studies should yield
significant basic information on the mechanisms of genetically
determined immunological disease, and provide additional animal
models for further research.

## Key facts

- **NIH application ID:** 3129743
- **Project number:** 5R01AI020232-06
- **Recipient organization:** JACKSON LABORATORY
- **SAM.gov UEI:** XR6LMXNKDJJ1
- **Principal Investigator:** CHARLES L SIDMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $143,999
- **Award type:** 5
- **Project period:** 1983-08-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129743

## Citation

> US National Institutes of Health, RePORTER application 3129743, MECHANISMS OF AUTOIMMUNITY (5R01AI020232-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129743. Licensed CC0.

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