# PATHOLOGY OF INBORN SKELETAL DISEASES

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1990 · $210,038

## Abstract

Inborn molecular defects in collagen structure are being characterized
in various skeletal diseases. The emphasis is on osteogenesis
imperfecta, Ehlers Danlos syndrome and certain chondrodystrophies. Of
particular interest are diseases that result in structural mutations of
collagen expressed in the extracellular matrix and their effects or
collagen polymerization and cross-linking. The application of micro-
techniques in protein chemistry to tissue biopsies is the theme of the
work.

The goal with osteogenesis imperfecta is to understand better how a
diversity of mutatiotis in type I collagen all result in brittle bone.
By studying bone tissue (surgery and autopsy) from patients of known
molecular defect, the degree to which mutations are expressed and
persist extracellularly in cross-linked bone matrix will be examined. Is
the disease principally one of collagen underproduction rather than the
consequences of structurally inadequate collagen molecules forming the
matrix? Likewise, the consequences of structural mutations and
post-translational defects of collagen in Ehlers-Danlos syndromes VI ind
VII will be defined in more detail.

Efforts will be made to reveal inherited structural defects in
cartilage-specific collagens (types II and IX) as the cause of curtain
forms of chondrodystrophy, including the broadly-defined
spondyloepiphyseal dysplasias and diastrophic dysplasias. The
possibility that polymorphisms of the human type II collagen gene exist
in the population, and perhaps account for observed natural variations
in degree of cross-linking in human cartilage collagen, will be tested.
Inherited mutations of type II collagen affecting cross-linking as a
cause of familial osteoarthrosis will also be examined.

The objective is to learn the importance of certain features of collagen
structure, for example those that control cross-linking reactions, in
determining function. Through an understanding of the effects of rare
inborn mutations, so the normal properties of collagens and their
variations can be better appreciated.

## Key facts

- **NIH application ID:** 3158036
- **Project number:** 5R01AR037318-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** David R Eyre
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $210,038
- **Award type:** 5
- **Project period:** 1986-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158036

## Citation

> US National Institutes of Health, RePORTER application 3158036, PATHOLOGY OF INBORN SKELETAL DISEASES (5R01AR037318-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158036. Licensed CC0.

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