Kleyn P W, Fan W, Kovats S G, Lee J J, Pulido J C, Wu Y, Berkemeier L R, Misumi D J, Holmgren L, Charlat O, Woolf E A, Tayber O, Brody T, Shu P, Hawkins F, Kennedy B, Baldini L, Ebeling C, Alperin G D, Deeds J, Lakey N D, Culpepper J, Chen H, Glücksmann-Kuis M A, Carlson G A, Duyk G M, Moore K J
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
Cell. 1996 Apr 19;85(2):281-90. doi: 10.1016/s0092-8674(00)81104-6.
The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 44 amino acids with 24 intron-encoded amino acids. The normal transcript appears to be abundantly expressed in the hypothalamus, a region of the brain involved in body weight regulation. Variation in the relative abundance of alternative splice products is observed between inbred mouse strains and appears to correlate with an intron length polymorphism. This allele of tub is a candidate for a previously reported diet-induced obesity quantitative trait locus on mouse chromosome 7.
通过定位克隆已鉴定出导致矮胖型肥胖表型的突变基因。剪接供体位点内的单个碱基变化导致成熟的tub mRNA转录本中单个内含子的错误保留。这种突变的结果是羧基末端的44个氨基酸被24个内含子编码的氨基酸取代。正常转录本似乎在下丘脑中大量表达，下丘脑是大脑中参与体重调节的区域。在近交系小鼠品系之间观察到可变剪接产物相对丰度的差异，并且似乎与内含子长度多态性相关。tub的这个等位基因是先前报道的位于小鼠7号染色体上的饮食诱导肥胖数量性状位点的候选基因。
