# TYPE I COLLAGEN BIOSYNTHESIS IN OSTEOGENESIS IMPERFECTA

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 1993 · $173,283

## Abstract

Osteogenesis imperfecta is a heritable disease of connective tissue that
results from a wide variety of mutations of type I collagen.  This grant
outlines a series of protocols designed to define these abnormalities at
the molecular level.  It is based on the assumption that it is easier to
define the mutations in collagen by studying the mRNA rather than its very
complex gene.  Fibroblasts derived from patients with 0I will be used as a
source of RNA.  Structural mutation of the alpha 1 or alpha 2 collegen mRNA
will be localized using a series of end-labeled S1 probes that encompass
the entire mRNA.  The probes will be derived from single-stranded cDNAs
cloned in M-13.  The exact mutation will be defined by dideoxy sequencing
of an extended cDNA initiated from a synthetic oligonucleotide primer
complementary to a region 3' to the region suggested of having the
abnormality as dictated by the S-1 protection experiments.  Another
oligo-nucleotide coding for the abnormal sequence will be constructed and
used as a mutation specific hybridization probe to precisely localize the
mutation to the gene.  Mutations which alter the steady state level of
collagen mRNA will be tested for an error of RNA processing using a novel
application of the M-13 derived hybridization probe.  This will involve an
S-1 protection protocol to detect an accumulation of a specific unspliced
mRNA, measurement of half-life of a normal and mutant cytoplasmic mRNA and
solution hybridization of radiolabeled RNA from in vitro transcribed
muclei.  The methods that are developed in this grant will have general
applicability to a wide variety of mutations involving type I collagen.
The mutation-specific oligonucleotides provide the means to rapidly detect
a subtle mutation in genomic DNA.  It has the potential to become a very
powerful adjuvant for the clinical geneticist who must counsel a family
with a connective tissue disorder.

## Key facts

- **NIH application ID:** 3155794
- **Project number:** 5R01AR030426-12
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **SAM.gov UEI:** H6D6JMXJXDE6
- **Principal Investigator:** David W. Rowe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $173,283
- **Award type:** 5
- **Project period:** 1982-04-01 → 1995-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155794

## Citation

> US National Institutes of Health, RePORTER application 3155794, TYPE I COLLAGEN BIOSYNTHESIS IN OSTEOGENESIS IMPERFECTA (5R01AR030426-12). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155794. Licensed CC0.

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