Zebrafish as a Model to Study NF1-Associated Learning Deficits

Abstract

Neurofibromatosis type 1 (NF1) is a genetic condition which affects one in 3,000 children and is known mostly because it causes light-brown patches of skin pigment, called cafe-au-lait spots, but also tumors that grow along nerves, called neurofibroma. A second aspect of NF1 is that the majority of children with NF1 develop cognitive deficits. The disorder is caused by mutations in a gene neurofibromin. In normal individuals, neurofibromin regulates the activity of another protein, called Ras, which controls cell divisions. In NF1 patients, the faulty neurofibromin gene fails to regulate Ras, which then tells cells to divide without stopping. Fortunately, only rarely do these tumors progress into malignant tumors. In contrast to the well understood mechanisms by which mutant neurofibromin fails to regulate Ras and hence cell divisions, why and how mutant neurofibromin leads to very prevalent learning disabilities is not well understood. Although the severity can vary widely from patient to patient, the majority of children with NF1 (up to 70%) have cognitive deficits, mostly attention deficits and learning disabilities. The long-term goals of this research grant proposal are to determine the mechanisms by which neurofibromin regulates learning, and to identify new drugs capable to antagonize learning deficits in an NF1 animal model.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2015
Accession Number
ADA620531

Entities

People

  • Michael Granto

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Animals
  • Biological Sciences
  • Cancer
  • Cells
  • Diseases And Disorders
  • Enzyme Inhibitors
  • Fish
  • Genetics
  • Medical Personnel
  • Neoplasms
  • Nervous System
  • Neurofibromatosis
  • Neuromuscular Diseases
  • Skin Diseases
  • Small Molecules
  • Students
  • Therapy

Fields of Study

  • Medicine

Readers

  • Artificial Intelligence
  • Molecular and Cellular Biology

Technology Areas

  • Biotechnology