Development of a new method to generate the model animal of human chromosomal disorders

2013 Fiscal Year Final Research Report

• Project/Area Number: 24650241
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: Institute of Physical and Chemical Research (2013); National Institute of Genetics (2012)
• Principal Investigator: TAMURA Masaru 独立行政法人理化学研究所, バイオリソースセンター, 開発研究員 (50370119)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: マウス / 染色体異常疾患 / トリソミー / モデル動物 / CRE/loxP / トランスポゾン

Research Abstract

It is estimated that over 1% of human newborn have some kind of chromosomal anomalies including partial trisomy. Although incidence of chromosomal abnormalities is high, molecular mechanisms and causative genes of chromosomal disorders remain unclear, because we have no animal model of most part of chromosomal diseases. In this study, we challenged the development of the new method that created the model animal of chromosomal disorders using the CRE/loxP technology and local hopping system of transposon. We inserted the loxP and Tol2 transposon into the mouse genome by transgenic or homologous recombination techniques. We obtained several transgenic mouse lines and ES cell lines, and established the platform to generate the model animal of chromosomal disorders. In addition, we tried to develop the new phenotyping method using the micro computed tomography and contrast agents. These new techniques will help us to understand the molecular mechanism of human chromosomal disorders.

Research Products

• [Journal Article] The Hand2 gene dosage effect in developmental defects and human congenital disorders (2014)
  • Author(s): Tamura M., Amano T. and Shiroishi T.
  • Journal Title: Curr. Top. Dev. Biol Volume: (in-press)
  • Peer Reviewed
• [Journal Article] Prdm9 polymorphism unveils mouse evolutionary tracks (2014)
  • Author(s): Kono H., Tamura M., Osada N., Suzuki H., Abe K., Moriwaki K., Ohta K. and Shiroishi T.
  • Journal Title: DNA Res Volume: (in-press)(PMID:24505791)
  • Peer Reviewed
• [Journal Article] Phenotype detection in morphological mutant mice using deformation features (2013)
  • Author(s): Roy S., Liang X., Kitamoto A., Tamura M., Shiroishi T. and Brown MS.
  • Journal Title: Med. Image Comput. Comput-Assist. Interv. Volume: 16(PMID:24505791) Pages: 437-444
  • Peer Reviewed
• [Journal Article] Functional conservation of Gsdma cluster genes specifically duplicated in the mouse genome (2013)
  • Author(s): Tanaka S., Mizushina Y., Kato Y., Tamura M. and Shiroishi T.
  • Journal Title: G3 : Genes, Genomes, Genetics Volume: 3(10) Pages: 1843-1850
  • DOI: 10.1534/g3.113.007393,PMID:23979942
  • Peer Reviewed
• [Journal Article] Over-dosage of Hand2 causes limb and heart defects in human chromosomal disorder, partial trisomy distal 4q (2013)
  • Author(s): Tamura M., Hosoya M., Fujita M., Iida T., Amano T., Maeno A., Kataoka T., Otsuka T., Tanaka S, Tomizawa S. and Shiroishi T.
  • Journal Title: Hum. Mol. Genet Volume: 22 Pages: 2471-2481
  • DOI: 10.1093/hmg/ddt099,PMID:23449628
  • Peer Reviewed
• [Presentation] マウスモデルを用いたヒト染色体異常疾患の解析 : ヒト4番染色体長腕部分重複症をモデルとして (2014)
  • Author(s): 田村勝,若菜茂晴,城石俊彦
  • Organizer: 第61回実験動物学会総会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 20140515-17
• [Presentation] X-Ray data (X-ray & micro-CT) (2013)
  • Author(s): Masaru Tamura, Yasuyo Kozawa, Kazuhiro Hirota, Toshihiko Shiroishi, Shigeharu Wakan
  • Organizer: International Mouse Phenotyping Consortium Phenotyping Workshop
  • Place of Presentation: CNR Headquarters, Rome, Italy
  • Year and Date: 20131202-04
• [Presentation] Micro-Computed Tomography (micro-CT)を用いた軟組織表現型高速イメージング (2013)
  • Author(s): 田村勝
  • Organizer: 日本遺伝学会第85回大会
  • Place of Presentation: 慶応大学
  • Year and Date: 20130919-21
• [Presentation] Micro-Computed Tomography (micro-CT)を用いたマウス形態計測 (2013)
  • Author(s): 田村勝
  • Organizer: 第60回実験動物学会総会ワークショップ<次世代マウス表現型解析技術の潮流>
  • Place of Presentation: つくば国際会議場
  • Year and Date: 20130515-17
• [Presentation] Micro-Computed Tomography (micro-CT)による軟組織高速イメージング (2013)
  • Author(s): 田村勝
  • Organizer: 第2回実験動物科学シンポジウム新たなライフサイエンス研究の展開?鳥類リソースの整備と活用に向けて-
  • Place of Presentation: 名古屋大学
  • Year and Date: 2013-12-09
  • Invited
• [Presentation] Introduction of Mouse phenotyping using the Micro Computed Tomography (2013)
  • Author(s): Masaru Tamura
  • Organizer: 2013 Asian Mouse Mutagenesis and Resource Association (AMMRA)/ Asia Mouse Phenotyping Consortium (AMPC) Annual Meeting and Workshop on Mouse Model Research
  • Place of Presentation: RIKEN BRC, Tsukuba, Japan
  • Year and Date: 2013-05-18
• [Presentation] ヒト4q-terに存在する複数遺伝子の量比は、頭蓋顔面骨形成に関与する (2012)
  • Author(s): 田村勝,城石俊彦
  • Organizer: 日本遺伝学会第84回大会
  • Place of Presentation: 九州大学
  • Year and Date: 20120920-22
• [Presentation] 組織をみる : 古典組織学VS Micro-Computed Tomography (2012)
  • Author(s): 田村勝
  • Organizer: 第25回モロシヌス研究会
  • Place of Presentation: 東京大学
  • Year and Date: 20120708-09
• [Book] 遺伝子図鑑(国立遺伝学研究所「遺伝子図鑑」編集委員会)10-2:動物の品種改良 (2013)
  • Author(s): 田村勝
  • Total Pages: 214-215
  • Publisher: 悠書館
• [Book] マウス実験の基礎知識第2版(小出剛編集)第5章:マウスの解剖について知ろう (2013)
  • Author(s): 田村勝
  • Total Pages: 67-78
  • Publisher: オーム社
• [Book] マウス実験の基礎知識第2版(小出剛編集)第6章:マウスの胎仔を見てみよう (2013)
  • Author(s): 田村勝,前野哲輝,天野孝紀
  • Total Pages: 79-92
  • Publisher: オーム社