2014 Fiscal Year Annual Research Report
| Project/Area Number |
14F04904
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| Research Institution | The University of Tokyo |
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Principal Investigator |
廣川 信隆 東京大学, 医学(系)研究科(研究院), 教授 (20010085)
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| Co-Investigator(Kenkyū-buntansha) |
ZHOU Ruyun 東京大学, 医学(系)研究科(研究院), 外国人特別研究員
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| Project Period (FY) |
2014-04-25 – 2016-03-31
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| Keywords | KIFs / knock-out mice / fear conditioning |
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| Outline of Annual Research Achievements |
In the previous research, we identified Kinesin superfamily protein 26A (KIF26A), KIF26A is a rather atypical member as it lacks ATPase activity. Mice with a homozygous deletion of Kif26a developed a megacolon with enteric nerve hyperplasia. Kif26a-/- enteric neurons showed hypersensitivity for GDNF-Ret signaling, and we found that KIF26A suppressed GDNF-Ret signaling by direct binding and inhibition of Grb2, an essential component of GDNF/Akt/ERK signaling (Zhou et al., Cell 139, 802-813, 2009).
To circumvent lethality and postnatally analyze the gene function of Kif26a, I generated Kif26a conditional KO mice. I used a rat synapsin promoter-driven Cre transgenic line (Syn-Cretg/d) (Zhu et al., 2001) and crossed Kif26a+/_;Syn-Cretg/d mice with Kif26afl/fl mice to obtain conditional KO mice (Kif26afl/_;Syn-Cretg/d). Kif26a conditional KO mice were confirmed by polymerase chain reaction (PCR) and western blotting.
Kif26a conditional KO mice appear to develop normally and fertile. First, 8-week old mice were analyzed using histological study, Hematoxylin-eosin (HE)-stained sections showed there was no gross anatomical defects of the brain in 8-week old mice. Using 3-6 month old mice, we are conducting a series of behavioral analyses, such as rotarod test, open field test, elevated plus maze test, Morris water maze test, fear conditioning. Primary substantia nigra neurons culture, immunohistochemical staining, neurochemical study, live imaging are also be studying to investigate the function of KIF26A in central nervous system.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
I focused on ENS function of KIF26A, but the functions of KIF26A in other systems remain unknown. I found in central nervous system KIF26A specifically expressed in substantia nigra by lacZ staining and that is much interesting as I thought.
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| Strategy for Future Research Activity |
More behavior tests will be conducted. Since some neuron diseases are degenerative disorders, for this reason, it is important to consider mouse to human age equivalents. Histological study, behavioral analyses, immunohistochemical staining and neurochemical study will be conducted at the ages of 1-year old, 18-month old mice and 24-month old mice, respectively.
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