# PHENOTYPIC ANALYSES OF GENETIC MYOPATHIES IN VITRO

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1989 · $198,506

## Abstract

The ultimate goal of these investigations is improved diagnosis
and treatment of heritable myopathies through elucidation of
underlying biochemical and genetic mechanisms.  Understanding
of these disorders requires correlation of phenotypic and genetic
information.  Phenotypic analyses of human myopathies in tissue
culture have been limited by the restricted size of diagnostic
muscle biopsies and the modest proliferative capacity of cultured
human muscle cells.  This laboratory has undertaken to overcome
these obstacles by establishing permanent myogenic cell lines
from biopsy material.  The primary focus will be the
mitochondrial encephalomyopathies, disorders of the electron
transport chain, some of which may result from mutations within
the 16,569 base pairs of the mitochondrial genome.  Collaborative
studies will be undertaken, also, of Duchenne muscular dystrophy,
DMD, whose gene has been localized within several hundred
thousand base pairs on the X-chromosome.

Preliminary results from this laboratory have demonstrated the
feasibility of obtaining human myogenic cell lines, established by
reversible transformation with the early region of SV40.  In other
studies defects of oxidative metabolism have been demonstrated
in differentiating muscle cultures from patients with
mitochondrial encephalomyopathies.  Other groups have
demonstrated a muscle-specific transcript encoded within the
putative DMD region of the X-chromosome.  This proposal seeks,
first, to improve establishment and maintenance of human
myogenic cell lines through modifications of the SV40 large T
antigen procedure and by transfection with other oncogenes, some
of which may extend proliferation of human myoblasts without
full transformation; second, to identify precisely the defective
component of the electron transport chain and the location of its
encoding gene, through studies of oxidative metabolism and
mitochondrial protein synthesis in cell lines from patients with
mitochondrial encephalomyopathies, and in cybrids (produced
from nuclei and cytoplasm of control and patient cell lines,
respectively); third, to study expression of putative DMD gene
sequences in Lyonized normal and DMD myogenic cell lines
established from DMD heterozygotes also heterozygous for the X-
linked marker enzyme, G6PD.  It is anticipated that permanent
myogenic cell lines will also prove useful for phenotypic analyses
of other heritable myopathies, expression of which may require
myogenic differentiation.

## Key facts

- **NIH application ID:** 3158477
- **Project number:** 5R01AR038231-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** OREST HURKO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $198,506
- **Award type:** 5
- **Project period:** 1987-08-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158477

## Citation

> US National Institutes of Health, RePORTER application 3158477, PHENOTYPIC ANALYSES OF GENETIC MYOPATHIES IN VITRO (5R01AR038231-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158477. Licensed CC0.

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