# GENETIC BASIS OF SYSTEMIC AUTOIMMUNITY

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1993 · $378,897

## Abstract

Despite years of studying human disease and animal models, the exact
mechanisms leading to autoimmunity are poorly defined.  Although these
diseases are considered multifactorial in origin, genetic factors are
undoubtedly the most important contributors.  Further understanding of
these complex syndromes requires definition of the number and nature of
the predisposing genes.  Advances in molecular genetic methodologies, such
as creation of linkage-maps, novel positional cloning techniques,
procedures for localizing genes to chromosomes and other methods, now make
this task feasible.  Using these techniques, identification of genes
associated with autoimmune diseases can be undertaken in a broad manner
rather than being restricted to certain suspected genes.  Such an approach
requires no prior knowledge of the genes, factors or mechanisms involved,
and focuses directly on the primary genetic contributions rather than
secondary or unrelated phenomena.

Our research has focused on the prototypic autoimmune disease, systemic
lupus erythematosus (SLE).  Given the heterogeneity of this disease and
the likely involvement of multiple genes, the task of identifying
predisposing genes in humans is presently immense, or even impossible.
Therefore, this research will be performed in inbred lupus-prone mice.  We
will create linkage-maps distinguishing selected autoimmune and non-
autoimmune mice primarily using simple chromosomal sequence length
polymorphic (SSLP) markers.  Backcrosses and F2 intercrosses between these
mice will be generated, and humoral and histopathologic autoimmune traits
with high penetrance will be assessed for their presence, severity, onset
and correlations.  Mice will then be typed with appropriate SSLP markers
and linkage analyses performed to determine the number and chromosomal
location of genes associated with each autoimmune trait.  Once autoimmune
loci are precisely mapped, identification of glomerulonephritis-associated
genes will be attempted by searching for known candidate genes in the
mouse (and human) genome.  Genes not thus identified will be sought by
positional cloning techniques. Creation of linkage maps and identification
of pleotropic or specific autoimmune trait-associated genes will
ultimately provide the means by which the molecular basis of lupus can be
defined.

## Key facts

- **NIH application ID:** 3159656
- **Project number:** 2R01AR039555-07
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** Argyrios N Theofilopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $378,897
- **Award type:** 2
- **Project period:** 1988-09-01 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159656

## Citation

> US National Institutes of Health, RePORTER application 3159656, GENETIC BASIS OF SYSTEMIC AUTOIMMUNITY (2R01AR039555-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159656. Licensed CC0.

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