MOLECULAR-CLONING AND CHARACTERIZATION OF ALTERNATIVELY SPLICED TRANSCRIPTS OF THE MOUSE NEUROFIBROMATOSIS-2 GENE

The human neurofibromatosis 2 (NF2) gene has recently been isolated an d predicted to encode a novel protein named merlin. Based on its high homology to the moesin-ezrin-radixin family of proteins, it may be inv olved in mediating interactions between the plasma membrane and the cy toskeleton. Here we report the isolation and characterization of multi ple transcript isoforms of the mouse NF2 gene. The full length coding complementary DNA sequence of transcript isoform I is 1788 base pairs in length, shares 90% sequence identity with the human NF2 complementa ry DNA, and encodes a putative protein of 596 amino acids sharing 98% homology with the human merlin protein. Transcript isoforms II and III carry a 45- and 16-base pair insertion, respectively, at nucleotide 1 740 at the 3' end, generated by two different modes of alternative spl icing; both insertions introduce premature termination codons. Thus, t ranscript isoforms II and III predict proteins of 591 and 584 amino ac ids with altered COOH-termini of more hydrophilic character as compare d to isoform I. Northern blot analysis and reverse transcription-polym erase chain reaction analysis indicate that the mouse NF2 gene is wide ly expressed in different tissue types and that the alternative transc ripts are variantly expressed. The results presented here indicate hig h conservation of the NF2 gene during evolution and suggest a possible role for the COOH-terminus in mouse merlin function.