Sahly I, Gogat K, Kobetz A, Marchant D, Menasche M, Castel M, Revah F, Dufier J, Guerre-Millo M, Abitbol M M
CERTO, Faculté Necker, 156 rue de Vaugirard, 75015 Paris, France and INSERM U465, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Hum Mol Genet. 1998 Sep;7(9):1437-47. doi: 10.1093/hmg/7.9.1437.
The tubby strain of mice exhibits maturity-onset obesity and sensory deficits in vision and hearing. The mutated 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 selectively 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 retina. 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 observations highlight similarities between CPE, prohormone convertases, several neuropeptides and tub gene expression patterns during embryogenesis, and may narrow down the avenues to explore in order to determine ultimately the function of the TUB protein.
肥胖型小鼠表现出成年期肥胖以及视觉和听觉方面的感觉缺陷。最近鉴定出了导致这种表型的突变基因tubby（tub），但尚未从其氨基酸序列推断出TUB蛋白的功能。这促使我们进行表达图谱研究，希望它们有助于阐明TUB蛋白的生物学作用。我们报告了通过Northern印迹法和原位杂交法（使用反义寡核苷酸探针）确定的tub基因在胚胎、胎儿和成年小鼠组织中的表达模式。在小鼠胚胎中，从受孕后9.5天开始，tub在中枢神经系统和外周神经系统中的分化神经元中选择性表达。在成年小鼠中，tub在几个主要脑区转录，包括大脑皮层、海马体、控制进食行为的下丘脑的几个核、内耳的螺旋神经节以及视网膜的光感受器细胞。这些结构包含由肥胖突变诱导的发病机制的潜在细胞靶点。神经元特异性的tub基因分布使得能够在肥胖型小鼠中建立基因型-表型相关性。这种相关性让人联想到在肥胖/肥胖小鼠中观察到的情况，其表型也以肥胖为特征，是由羧肽酶E（CPE）基因的无效突变引起的。我们的观察结果突出了胚胎发育过程中CPE、激素原转化酶、几种神经肽和tub基因表达模式之间的相似性，并可能缩小最终确定TUB蛋白功能所需探索的途径范围。
