The murine NF2 homologue encodes a highly conserved merlin protein with alternative forms

Abstract

The recently isolated gene for neuroflbromatosls type 2 (NF2) encodes a 595 amlno acid protein, named merlin, which Is related to the cytoskeleton-assoclated proteins moesln, ezrin and radlxin. To Identify evolutionarily conserved regions and to provide sequence Information necessary for the establishment of a mouse model for NF2, we have determined the cDNA sequence of the mouse NF2 tumor suppressor gene, and mapped It In the mouse genome. Mouse merlin is a 596 amino acid protein, 98% identical to human merlin, but one amlno acid longer due to the Insertion of a proline residue near the C-terminus. Of the nine amlno acid differences between mouse and humans, seven occur in the C-termlnal 20% of the protein, far from the protein 4. 1 domain that defines this family. Two of the NF2 cDNA clones reveal evidence of alternative splicing events that alter the predicted merlin product, one removing a 45 amlno acid segment from the middle section of the protein and the other changing the C-terminus. The existence of several different forms of merlin potentially with different primary roles will complicate the Identification of the precise function that must be disrupted to cause the NF2-assoclated tumors. The mouse NF2 homologue maps to Chr 11, in a region homologous to human Chr 22, but devoid of any mouse mutations which could be models of the human disorder.