PROMINENT NEURONAL-SPECIFIC TUB GENE-EXPRESSION IN CELLULAR TARGETS OF TUBBY MICE MUTATION

The tubby strain of mice exhibits maturity-onset obesity and sensory d eficits in vision and hearing, The mutated gene, tub, responsible for this phenotype was identified recently, but the function of the TUB pr otein has not been deduced from its amino acid sequence, This prompted us to undertake expression mapping studies with the hope that they mi ght help to elucidate the biological role of the TUB protein. We repor t the tub gene expression pattern in embryonic, fetal and adult mice t issues as determined by northern blots and in situ hybridization, usin g antisense oligonucleotidic probes, In mouse embryos, tub is expresse d selectively in differentiating neurons of the ensemble of central an d peripheral nervous systems, starting at 9.5 days after conception, I n adult mice, tub is transcribed in several major brain areas, includi ng cerebral cortex, hippocampus, several nuclei of the hypothalamus co ntrolling feeding behavior, in the spiral ganglion of the inner ear an d in the photoreceptor cells of the retina, These structures contain p otential cellular targets of the tubby mutation-induced pathogenesis. The neuronal-specific tub gene distribution allows the establishment o f a genotype-phenotype correlation in the tubby mice, This correlation is reminiscent of that observed in fat/fat mice, whose phenotype, als o characterized by obesity, is caused by a null mutation in the carbox ypeptidase E (CPE) gene, Our observations highlight similarities betwe en CPE, prohormone convertases, several neuropeptides and tub gene exp ression patterns during embryogenesis, and may narrow down the avenues to explore in order to determine ultimately the function of the TUB p rotein.