| 研究実績の概要 |
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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| 今後の研究の推進方策 |
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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