NEUROFIBROMATOSIS AS A MODEL OF HUMAN NF

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from Applicant's Abstract): Neurofibromatosis type
1 (NF1) is one of the most common genetic disorders in man, with an
incidence rate of roughly 1 in 3,000 births. The study of how mutations
and resulting alterations in cell function lead to the development of
neurofibromas and other features of NF1 will require systems that can be
experimentally manipulated. Damselfish neurofibromatosis (DNF), a disease
affecting bicolor dameselfish is the only naturally occurring animal model
of neurofibromatosis. This disease consists of plexiform neurofibromas and
malignant schwannomas, many of which are hyperpigmented. DNF is caused by
a transmissible, filterable agent. Cell cultures of tumor derived cells
contain 100nm round particles and exhibit reverse transcriptase activity
suggesting that DNF is associated with a retrovirus. The transmissible
etiology of DNF results in a tumor model system that is easily manipulated
in the laboratory. This research will emphasize characterization of the
etiologic agent of DNF and the use of this agent as a tool to understand
the pathogenesis of NF1 through five closely related research projects: 1)
The morphology, nucleic acid content, protein composition, and reverse
transcriptase activity of the viral particles associated with DNF
(tentatively termed damselfish neurofibromatosis virus or DNFV) will be
characterized. 2) Materials and methods will be developed to allow the
detection of serum antibodies to DNFV as well as viral proteins and
nucleic acids in tissues and in cultured cells from these fish. 3) The
relationship between DNFV and neurofibroma development in these fish will
be evaluated using transmission experiments in combination with probes
developed in this study to screen for the presence of DNFV. 4) Studies of
the pathogenesis of DNF will be continued and expanded using detection
systems for DNFV as tracers of the cells types infected at various stages
of spontaneous and experimentally induced tumor development. 5) Membrane
properties of Schwann cells isolated from normal nerves and neurofibromas
will be assessed and compared using electrophysiological techniques to
determine if alterations occur during tumorigenesis or as a result of
infection of Schwann cells with DNFV. If difference in ionic currents are
found, pharmacologic techniques will be used to assess the involvement of
GTP-binding protein mediated second messenger systems in these
alterations. Information concerning alterations of membrane properties in
neurofibroma derived cells should contribute to understanding of the axon-
Schwann cell interaction and how this is altered during NF1 tumorigenesis.
The usefulness of oncogenic viruses as experimenal tools for investigation
of mechanisms of carcinogenesis has been well documented. The
investigators believe that DNF will provide a useful experimental system
to study the biology of neurofibromas and that their findings will be
relevant to understanding the pathogenesis of NF1 in man.
StatusFinished
Effective start/end date1/1/909/29/97

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.