Characterization of Neurofibromas of the Skin and Spinal Roots in a Mouse Model
Abstract
Benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) contribute to the majority of morbidity and mortality associated with NF1. The proposed studies will provide significant insight into one of the fundamental questions in neurofibroma biology: whether bi-allelic NF1 inactivation is necessary for neurofibroma formation. The objectives of this proposal are to use a newly established mouse model to (1) identify and characterize neurofibromas that are exclusively or predominantly comprised of NF1+/- cells (designated NF1+/- neurofibromas hereafter) in the skin and spinal roots; and (2) determine whether in this model, neurofibromas in the skin are similar to human dermal neurofibromas and thus are fundamentally different from the plexiform neurofibromas found in spinal roots. Previous studies of human tumors suggest that dermal and plexiform neurofibromas have fundamental differences in their dependence on the NF1 hetereozygous environment and have different malignant transformation potentials. We have made substantial progress in the first two years of the award. For Task 1, we demonstrated that bi-allelic inactivation of Nf1 in neural crest stem cells is required for neurofibroma formation. These results resulted in publication of 3 manuscripts this year (see appendices). For Task 2, we have determined that the Nf1 heterozygous environment promotes neurofibroma progression, but is not required for tumor initiation. We are currently writing a manuscript to publish these results. For Task 3, we have generated the half of the mutant mice proposed for the study. The preliminary data suggest that the NF1 heterozygous environment is not essential for malignant transformation. This year, we will finish characterizing tumor phenotypes of these mutant mice and generate more mutants for analysis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2008
- Accession Number
- ADA483297
Entities
People
- Yuan Zhu
Organizations
- University of Michigan