THE MOLECULAR-BASIS OF THE OBESE MUTATION IN OB(2J) MICE

The recessive ob(2J) mutation in mice results in an obese phenotype th at is identical to that of the original ob allele. Initial studies ind icated that ob(2J) mice fail to synthesize ob RNA in adipose tissue. H ere we report the genomic organization of the mouse obese gene and est ablish the molecular genetic basis of the ob(2J) mutation. The ob(2J) mutation is the result of the insertion of a retroviral-like tranposon in the first intron of the oh gene. The insertion is a member of the ETn family of transposons and contains several splice acceptor and pol yadenylation sites. This leads to the production of chimeric RNAs in w hich the ob first exon is spliced to sequences in the ETn insertion. A s a consequence mature ob RNA is not synthesized, and leptin, the enco ded protein, is not produced. (C) 1997 Academic Press.