2 DOMINANT MUTATIONS IN THE MOUSE FUSED GENE ARE THE RESULT OF TRANSPOSON INSERTIONS

The mouse Fused locus encodes a protein that has been implicated in th e regulation of embryonic axis formation. The protein, which has been named Axin to distinguish it from the product of the unrelated Drosoph ila melanogaster gene fused, contains regions of similarity to the RGS (regulators of G-protein signaling) family of proteins as well as to dishevelled, a protein that acts downstream of Wingless in D. melanoga ster. Loss-of-function mutations at Fused lead to lethality between da ys 8 and 10 of gestation. Three dominant mutations result in a kinked tail in heterozygotes. Two of the dominant mutations, Fused and Knobbl y, result from insertions of intracisternal A particle retrotransposon s into the gene. The insertion in Fused, within the sixth intron, crea tes a gene that produces wild-type transcripts as well as mutant trans cripts that initiate at both the authentic promoter and the 3'-most lo ng terminal repeat of the insertion. Knobbly, an insertion of the retr otransposon into exon 7, precludes the production of wild-type protein . Thus the Fused homozygote is viable whereas Knobbly is a recessive e mbryonic lethal. In both mutants the dominant kink-tailed phenotype is likely to result from the synthesis of similar amino-terminal fragmen ts of Axin protein that would contain the RGS domain, but lack the dis hevelled domain.