Utilization of a NF2-Mutant Mouse Strain to Investigate the Cellular and Molecular Function of the NF2 Tumor Suppressor Merlin
Abstract
Neurfibromatosis type 2 (NF2) is a familial cancer syndrome that features the development of nervous system tumors. The NF2-encoded protein, merlin, localizes to the membrane cytoskeleton interface, which is an unusual physical niche for a tumor suppressor. To generate an animal model for NF2 and to build the foundation for delineating the molecular function of merlin, we established a Nf2-mutant mouse strain through genetic engineering. Nf2+/- mice develop a spectrum of tumors that is distinct from that of their human counterparts, including osteosarcomas and hepatocellular carcinomas, which exhibit loss of the wild-type Nf2 allele. Embryos that are homozygous for a null Nf2 mutation fail to gastrulate, while chimeric embryos partially composed of Nf2-/-cells develop additional defects, including during cardiac development. Together, these observations indicate a requirement for merlin function in several different cell types in the mouse. The study of Nf2 function in these cell types formed the basis of this proposal. The following report describes our accumulating data that indicates an important and general role for NF2 function in cell differentiation. In addition, data from these and other studies in our laboratory point to a general role for merlin function in cell:cell communication in many cell types.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA420954
Entities
People
- Andrea I McClatchey
Organizations
- Massachusetts General Hospital