Down-regulation of dopamine transporter and abnormal behavior in STAT6-deficient mice.
To determine the role of STAT6 transcription factors in brain function, we performed a battery of mouse behavioral analyses of STAT6-deficient mice and made comparisons with wild-type mice. STAT6-deficient mice were significantly more hyperactive in the final two blocks of an open field test, indicating abnormal habituation in completing the task. Two learning tasks, a water maze and a passive avoidance test, were mastered by STAT6-deficient mice as effectively as the wild-type. RT-PCR analysis suggested that the levels of dopamine transporter (DAT) mRNA may be lower in the midbrain of the mutant. In agreement with the finding, subsequent Western blotting and immunohistochemical analysis demonstrated lower levels of DAT protein in the mutant striatum. These results lead to the proposal that, in addition to being a pivotal transcription factor in the immune system, STAT6 may be crucially implicated in mouse behavior by modulating the expression of neuronal genes such as DAT.
Yukawa
Kazunori
K
Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan. kazu59@wakayama-med.ac.jp
Iso
Hiroyuki
H
Tanaka
Tetsuji
T
Tsubota
Yuji
Y
Owada-Makabe
Kyoko
K
Bai
Tao
T
Takeda
Kiyoshi
K
Akira
Shizuo
S
Maeda
Masanobu
M
D000818:Animals; D001362:Avoidance Learning; D050483:Dopamine Plasma Membrane Transport Proteins; D015536:Down-Regulation; D018782:Maze Learning; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050800:STAT6 Transcription Factor; C493215:Slc6a3 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators