| 研究実績の概要 |
Fear is a basic emotion that enhances animal survival by triggering appropriate defensive responses (e.g. freeze, fight or flight) to perceived danger. However, irrational fears are linked to a variety of mental illnesses, such as phobia, anxiety, depression, PTSD etc. The molecular mechanism of fear is unclear. To this end, we performed a novel predator odor-based “innate fear” forward genetic screen, and identified a recessive Fear2m/m mutant that exhibited “fearless” phenotype and a dominant Popcornm/+ mutant that exhibited excessive “fearful” phenotype in the presence of predator odor.
For Fear2m/m mutant mice, we carried out a set of behavior, brain c-fos mapping, tissue-specific lesion and AAV-fear2 rescue experiments, and made the novel findings that Fear2 may function as a chemosensor for predator odor, and the trigeminal system besides olfactory plays important roles in predator odor-evoked innate fear/defensive behaviors. Our results will be published in the journal Nature Communications (accepted).
For putative fearful Popcorn m/+ mutant mice, we conducted several classical anxiety tests and sleep recording. In addition, we generated Popcorn m/+ mice by CRISPR/Cas9 technology to further verify the causality of the Popcorn mutation for the “fearful” phenotype.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
We have an excellent research team and received great help from outstanding collaborators.
We collaborated with Dr. Bruce Beutler at UT Southwestern Medical Center, and identified our recessive fearless Fear2m/m mutant mice using his ENU mutant mice generated for his immune screen. We collaborated with Drs. Ko Kobayakawa and Reiko Kobayakawa who are pioneers in the innate fear research, Dr. Takehashi Sakurai who is an outstanding neuroscientist, and made novel findings which will be published in high-profile journal.
Research on Popcorn m/+ mutant mice had been conducted as in the research proposal.
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