# COLLAGEN METABOLISM IN A MODEL FOR SCLERODERMA

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1989 · $101,980

## Abstract

Scleroderma (PSS) is a serious disease of unknown cause
characterized by excessive accumulation of collagen and other
connective tissue components in skin and internal organs.  The
mechanisms responsible for such accumulation are not known.  In
previous work form our laboratories we have demonstrated that
the TSK (tight skin) mutant mouse strain displays connective
tissue abnormalities that closely resemble those present in
patients with PSS including increased collagen tissue deposition,
and increased biosynthesis in skin organ cultures and cultured
fibroblasts.  Furthermore, we demonstrated a coordinated
increase in the levels of Types I and III collagen mRNAS these
cells.  These results suggests that the TSK mice are an ideal
experimental model for study of the connective tissue alterations
in PSS.  The purpose of the work proposed in this application will
be to continue our in depth and exhaustive studies of the
mechanisms responsible for the connective tissue alterations
displayed by TSK mice.  Particular emphasis will be placed on the
study of the regulation of collagen synthesis in TSK cultured
fibroblasts applying STATE of the ART biosynthetic and
biochemical methods as well as recently developed recombinant
DNA techniques currently used in our laboratories.  We will
examine the mechanisms responsible for increased collagen gene
expression by measuring transcription rates and mRNA stability.
In addition, we will attempt to identify regulatory defects by
mapping pertinent regions of one collagen gene by nuclease
sensitivity and by transient transfection experiments utilizing a
shuttle vector to introduce normal and deleted putative
regulatory sequences into normal and TSK fibroblasts.
Biosynthesis of collagen in skin organ cultures and tissue cultures
from normal and TSK dermal fibroblasts will be continued and the
biosynthesized products will be characterized.  Differences in the
content or structure of the various components present in the
tissues or synthesized in the TSK cultures will be identified.
Special emphasis will be placed on the identification of the minor
collagen types (V and VI) present and in the quantitation of their
relative proportions.  Several other differences in the biological
characteristics of normal and TSK cells and tissues will be
explored in further detail.  It is expected that the knowledge
gained from these studies will be of direct relevance to
understand the pathogenesis of the excessive collagen deposition
characteristic of PSS and will permit a more rational approach to
develop possible modes of therapy for this incurable and
devastating disease.

## Key facts

- **NIH application ID:** 3156339
- **Project number:** 5R01AR032564-05
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** SERGIO A JIMENEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $101,980
- **Award type:** 5
- **Project period:** 1988-04-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156339

## Citation

> US National Institutes of Health, RePORTER application 3156339, COLLAGEN METABOLISM IN A MODEL FOR SCLERODERMA (5R01AR032564-05). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156339. Licensed CC0.

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