2017 Fiscal Year Research-status Report
| Project/Area Number |
17K08133
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
曹 麗琴 筑波大学, 国際統合睡眠医科学研究機構, 助教 (60399475)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
クレウエ・ネベニウス ダニエラ 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60737667)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Keywords | 先天的恐怖 / 恐怖感情 / 精神疾患 |
|---|
| Outline of Annual Research Achievements |
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.
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
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.
|
| Strategy for Future Research Activity |
1.To examine expression pattern of Popcorn gene in mouse brain by in situ hybridization.
2.To conduct whole brain c-fos mapping to examine where Popcorn may act in the brain
3.To perform physiological and more behavior assays to determine whether Popcorn is a “fearful” mutant.
|
| Causes of Carryover |
Some expensive reagents and apparatus for the experiments will be purchased in FY2018
|
