演題詳細
Poster
分子,生化学、遺伝学的手法
Molecular, Biochemical, and Genetic Techniques
開催日 | 2014/9/12 |
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時間 | 11:00 - 12:00 |
会場 | Poster / Exhibition(Event Hall B) |
Mutatorマウスの継代から産まれた「ヒト可聴音域で鳴くマウス」
A singing strain in mutants from mutator mouse breeding
- P2-377
- 八木 健 / Takeshi Yagi:1 樋口 真弓 / Mayumi Higuchi:1 水口 洋平 / Yohei Minakuchi:2 豊田 敦 / Atsushi Toyoda:2 藤山 秋佐夫 / Asao Fujiyama:2 三浦 郁生 / Ikuo Miura:3 若菜 茂晴 / Shigeharu Wakana:3 内村 有邦 / Arikuni Uchimura:1
- 1:大阪大学大学院 / Grad. Sch. of Frontier Biosci., Osaka Univ. 2:国立遺伝学研究所 生命情報研究センター 比較ゲノム解析研究室 / Comparative Genomics Laboratory, National Institute of Genetics 3:マウス表現型解析開発チーム (独)理化学研究所・バイオリソースセンター / Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Forward genetics is essential to understand molecular functions in vivo. In mouse model, chemical mutagen, ENU (N-ethyl-N-nitrosourea), is widely used to induce mutations. However, since the number of introduced mutation is restricted (about 3,000 mutations / mouse) in ENU treated mice, massive screening of mutagenized mice is required to obtain desired mutant mice. We created new forward genetics model, where more mutations were accumulated in a mouse than a ENU treatment. We bred mutator mice, of which endogenous mutation rate was increased by modification of DNA polymerase δ involved in DNA replication, for a long time and generated more than 500 mutations per generation on entire genome. Thus, we could accumulate more than 6,500 mutations in the 20-generation bred mutator mice. We have established more than 20 independent inbreeding lines. So far, we obtained many mutants (dysmorphic mutants, disease-like mutants, behavioral mutants etc.) from our visible screening of the long-term bred mice. Most notable mutant was a singing (sng) mutant, which exhibited human audible vocalization after sex maturation. We identified the causative mutation in sng mutants and confirmed it by a creation of mice harboring the same mutation. Our established new forward genetics model might have a great potential to uncover molecular functions in neuroscience.