The Use of NF1 and NF2 Mutant Mouse Strains in the Investigation of Gene Function and Disease Development
Abstract
Gene targeting in mouse embryonic stem cells was; used to generate animal models for the human diseases NFl and NF2. Chimeric mice composed in part of Nfl-/- cells develop neurofibroma-like lesions that contain cells with Schwannian and perineurial features, which are Nfl-deficient. This model supports the view that neurofibromas develop in response to full loss of NFl function, and indicate that the target cell may be a neural crest derived precursor to the Schwann cell. A second model associated with Nfl mutation has been developed through the introduction of a linked mutation in the p53 gene. These animals rapidly develop tumors, a high percentage of which show features of malignant peripheral nerve sheath tumors (MPNSTs). Importantly, human NFl patients also develop MPNSTs at high frequency, and these tumors often carry p53 mutations as well. The Nf/p53 mutant mice are being studied for possible genetic modifier effects through crossing to other mouse strains.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADB243021
Entities
People
- Tyler Jacks
Organizations
- Massachusetts Institute of Technology