Generation of smooth musclc-specific mutagenesis in mice by using Cre/loxP targeting system

使用 Cre/loxP 靶向系统在小鼠中产生平滑肌特异性诱变

• 批准号: 10670107
• 负责人: TAKAHASHI Katsuhito
• 金额: $ 2.11万
• 依托单位: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670107/
• 关键词: Calponin; SM22; Transgenic mouse; Vascular smooth muscle; Cre; loxP; 平滑筋特異遺伝子; loxPシステム

Conditional mutant mice by the Cre/loxP recombination systems are promising for studying tissue-specific gene function and for making better models of human diseases. We have generated transgenic mouse lines expressing Cre-recombinase under the control of the SMC-specific human SM22 gene promoter (SM22/Ncre Tg). We have also engineered transgenic mice expressing a loxP-flanked CAT transgene reporter under the control of CAG promoter (CAT-Z Tg). The transgene contains lacZ reporter gene downstream of the loxP-flanked CAT sequence. When SM22/Ncre Tg and CAT-Z Tg mice were crossed, specific recombination and expression of lacZ was detected in heart at embryonic days 10.5-12.5 and later in vascular smooth muscle systems. SM22 promoter-mediated expression of lacZ was confined preferentially in areterial smooth muscle cells. The mice will be used to study the effects of various mutations in embryonic heart as well as in arterial SMC.

Cre/loxP重组系统的条件突变小鼠有望用于研究组织特异性基因功能和建立更好的人类疾病模型。在SMC特异性人SM22基因启动子(SM22/Ncre TG)的控制下，我们获得了表达Cre重组酶的转基因小鼠。我们还在CAG启动子(CAT-Z TG)的控制下，设计了表达loxP侧翼CAT转基因报告基因的转基因小鼠。该转基因在loxP侧翼CAT序列下游含有LacZ报告基因。当SM22/Ncre TG和CAT-Z TG小鼠杂交时，LacZ在胚胎10.5-12.5天的心脏中被检测到特异性的重组和表达，随后在血管平滑肌系统中被检测到。SM22启动子介导的LacZ基因的表达主要局限于血管平滑肌细胞。这些小鼠将被用来研究胚胎心脏和动脉SMC中各种突变的影响。

项目成果

Hideki Yoshikawa, Katsuhito Takahashi et al.: "Mice lacking smooth muscle calponin display increased bone formation that is"Cenes to Cells. 3. 685-695 (1998)

Hideki Yoshikawa、Katsuhito Takahashi 等人：“缺乏平滑肌钙调蛋白的小鼠表现出骨形成增加，即”Cenes to Cells。

Hisako Yamamura, Katsuhito Takahashi. et al.: "Expression of the smooth muscle calponin gene in human osteosarcoma and its"International Journal of Cancer. 79. 245-250 (1998)

山村久子、高桥胜人。

Hisako Yamamura, Katsuhito Takahashi, et al.: "Expression of the smooth muscle calponin gene in human osteosarcoma and its"International Journal of Cancer. 79. 245-250 (1998)

Hisako Yamamura、Katsuhito Takahashi 等人：“平滑肌钙调蛋白基因在人骨肉瘤及其中的表达”国际癌症杂志。

Tohru Sugimoto, Tohru Sugimoto, Hajime Hosoi, Yoshihiro Horii, Hiroyuki Ishida, Hitoshi Mine, Katsuhito Takahashi, Tatsuo Abem, Shigeru Ohta, Tadashi Sawada: "A malignant rhabdoido-tumor cell line showing neural and smooth muscle cell phenotypes"Internati

Tohru Sugimoto、Tohru Sugimoto、Hajime Hosoi、Yoshihiro Horii、Hiroyuki Ishida、Hitoshi Mine、Katsuhito Takahashi、Tatsuo Abem、Shigeru Ohta、Tadashi Sawada：“显示神经和平滑肌细胞表型的恶性横纹肌瘤细胞系”Internati

Christoopher A. Parker, Katsuhito Takahashi, et al.: "Cytoskeletal targeting of calponin in differentiated, contractile smooth muscle cells"Journal of Physiology (London). 508. 187-198 (1998)

Christopher A. Parker、Katsuhito Takahashi 等人：“分化的收缩平滑肌细胞中钙调蛋白的细胞骨架靶向”生理学杂志（伦敦）。