Accession Number:

ADB264003

Title:

Wounding-Induced Manifestations of Type 1 Neurofibromatosis

Descriptive Note:

Annual rept. 15 Sep 1998-14 Sep 1999

Corporate Author:

CINCINNATI UNIV OH

Personal Author(s):

Report Date:

1999-10-01

Pagination or Media Count:

79.0

Abstract:

Humans with mutations in the NF1 gene develop benign peripheral nerve tumors comprised mainly of Schwann cells neurofibromas and hyperpigmented spots on the skin CALM. Mice with mutations of the NF1 gene fail to develop CALM or neurofibromas. We cut the sciatic nerve of NF1nfl mice and induced frequent CALM- and rare neurofibroma-like lesions. We hypothesized that nerve lesion creates an environment that triggers abnormal behavior of heterozygous cells, including Schwann cells. We proposed to test this hypothesis using nerve grafting. Our data shows that mutant Schwann cells secrete factors that cause melanocyte pigmentation, and that, in addition, subpopulations of mutant Schwann cells transdifferentiate into pigment-forming cells in the wound environment. We also wounded NF1nf1 mice in a chemical carcinogenesis paradigm and obtained mice with increased pigmentation and keratinocyte tumors, further substantiating our hypothesis that a wound environment can trigger features of human NF1 disease. Finally, using transgenic mice, we proposed testing whether Ras activation in peripheral nerve Schwann cells is necessary andor sufficient to promote wound-associated phenotypes of NF1nf1 mice. Using a promoter that drives robust Schwann cell expression, we cloned constructs into the new promoter- driven plasmids, and have identified several founder mice.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE