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Journal of Biochemistry Advance Access originally published online on December 13, 2007
Journal of Biochemistry 2008 143(3):407-416; doi:10.1093/jb/mvm235
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© 2007 The Japanese Biochemical Society.

The Medaka FoxP2, a Homologue of Human Language Gene FOXP2, has a Diverged Structure and Function

Tatsuo Itakura1, Abhishek Chandra1, Zhi Yang1, XiaoDong Xue1, Bo Wang1, Wataru Kimura1, Keisuke Hikosaka1, Keiji Inohaya2, Akira Kudo2, Tadayoshi Uezato1 and Naoyuki Miura1,*

1Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192; and 2Department of Biological Information, Tokyo Institute of Technology, Yokohama 226-8501, Japan

*To whom correspondence should be addressed. Tel: +81 53 435 2325, Fax: +81 53 435 2369, E-mail: nmiura{at}hama-med.ac.jp

Received October 13, 2007; Accepted November 22, 2007


   Abstract

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.

Key Words: forkhead domain, FoxP2, language gene, medaka, molecular evolution

Abbreviations: DAPI, 4,6-Diamidino-2-phenylindole; dpf, days post-fertilization; EST, expression sequence tag; HRP, horseradish peroxidase; hpf, hours post-fertilization; IPTG, isopropyl-β-d-thiogalactopyranoside; PBS, phosphate-buffered saline


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