Utilization of a NF2-Mutant Mouse Strain to Investigate the Cellular and Molecular Function of the NF2 Tumor Suppressor, Merlin
Abstract
Neurofibromatosis 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 raising the intriguing question of how a protein that occupies such a physical niche controls cell proliferation. 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 N2 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 research proposal. The following report describes progress in studying merlin function during ES cell differentiation, in cardiomyocyte specification and in liver cells. Moreover, we have established an efficient and unique system for studying merlin and ERM function in the liver in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA387918
Entities
People
- Andrea I McClatchey
Organizations
- Massachusetts General Hospital