Itakura Tatsuo, Chandra Abhishek, Yang Zhi, Xue Xiaodong, Wang Bo, Kimura Wataru, Hikosaka Keisuke, Inohaya Keiji, Kudo Akira, Uezato Tadayoshi, Miura Naoyuki
Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu, Japan.
J Biochem. 2008 Mar;143(3):407-16. doi: 10.1093/jb/mvm235. Epub 2007 Dec 13.
Forkhead box (Fox) genes are involved in organogenesis and cell differentiation. A mutation of FOXP2 was discovered in patients with severe defects in speech and language. The medaka FoxP2 was cloned in order to clarify the molecular evolution and difference in the protein structure and function by comparing human/mouse and medaka genes. The result showed that medaka FoxP2 had a 73.7% homology to the human and mouse counterparts, and its zinc finger, leucine zipper and forkhead domain structures were conserved. However, medaka FoxP2 lacked a long polyglutamine repeat and had two insertions of unique amino acid sequences. FoxP2 expression was found in the epiphysis and retina, in addition to the midbrain and cerebellum. The transcriptional assay revealed that medaka FoxP2 showed a very weak repressive activity to the CC10 promoter while mouse Foxp2 exhibited a strong repressive activity. Mutational analyses of medaka FoxP2 showed that the three amino acids of forkhead domain were responsible for the weak repressive activity. These results suggest that medaka FoxP2 may play a different function in the development of the medaka fish.
叉头框（Fox）基因参与器官形成和细胞分化。在患有严重言语和语言缺陷的患者中发现了FOXP2突变。为了通过比较人类/小鼠和青鳉基因来阐明分子进化以及蛋白质结构和功能的差异，克隆了青鳉FoxP2。结果表明，青鳉FoxP2与人类和小鼠的对应物具有73.7%的同源性，其锌指、亮氨酸拉链和叉头结构域结构保守。然而，青鳉FoxP2缺乏长的聚谷氨酰胺重复序列，并且有两个独特氨基酸序列的插入。除中脑和小脑外，在松果体和视网膜中也发现了FoxP2表达。转录分析表明，青鳉FoxP2对CC10启动子表现出非常弱的抑制活性，而小鼠Foxp2表现出强抑制活性。青鳉FoxP2的突变分析表明，叉头结构域的三个氨基酸负责这种弱抑制活性。这些结果表明，青鳉FoxP2可能在青鳉鱼的发育中发挥不同的功能。
