Prominent neuronal-specific tub gene expression in cellular targets of tubby mice mutation. Hum Mol Genet 7

The tubby strain of mice exhibits maturity-onset obes-ity and sensory deficits in vision and hearing. The mu-tated gene, tub, responsible for this phenotype was identified recently, but the function of the TUB protein has not been deduced from its amino acid sequence. This prompted us to undertake expression mapping studies with the hope that they might help to elucidate the biological role of the TUB protein. We report the tub gene expression pattern in embryonic, fetal and adult mice tissues as determined by northern blots and in situ hybridization, using antisense oligonucleotidic probes. In mouse embryos, tub is expressed selective-ly in differentiating neurons of the ensemble of central and peripheral nervous systems, starting at 9.5 days after conception. In adult mice, tub is transcribed in several major brain areas, including cerebral cortex, hippocampus, several nuclei of the hypothalamus controlling feeding behavior, in the spiral ganglion of the inner ear and in the photoreceptor cells of the ret-ina. These structures contain potential cellular targets of the tubby mutation-induced pathogenesis. The neuronal-specific tub gene distribution allows the establishment of a genotype–phenotype correlation in the tubby mice. This correlation is reminiscent of that observed in fat/fat mice, whose phenotype, also characterized by obesity, is caused by a null mutation in the carboxypeptidase E (CPE) gene. Our observa-tions highlight similarities between CPE, prohormone convertases, several neuropeptides and tub gene ex-pression patterns during embryogenesis, and may narrow down the avenues to explore in order to deter-mine ultimately the function of the TUB protein