Production of Animal Models for Marbling by Introducing The Bovine ADAM12 Gene

导入牛 ADAM12 基因建立大理石花纹动物模型

• 批准号: 17580255
• 负责人: TANIGUCHI Yukio
• 金额: $ 2.3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17580255/
• 关键词: cattle; marbling; ADAM12; transgenic mouse; muscle; fat

ADAM12 is a member of the ADAM (a disintegrin and metalloprotease) family, and recently has been suggested to function in regulation of myogenesis and adipogenesis. It is also reported that the transgenic mice expressing human ADAM12 specifically in muscle tissue exhibit the intramuscular fat deposition. As these phenotypes are similar to the beef marbling, we produced the transgenic mice expressing the bovine ADAM12 gene specifically in muscle tissue to establish the animal models for marbling.Three transgenes (MCK-bADAM12 C3, TRC and MP) were prepared from the bovine ADAM12 cDNA. MCK-bADAM12 C3 encodes a membrane-anchored ADAM12 protein consisting of the prodomain, the metalloprotasase, disintegrin, cystein-rich, and transmenbrane domains and cytoplasmic-tail. MCK-bADAM12 TRC encodes a secreted-form protein consisting of the whole extracellular domain. MCK-bADAM12 MP encodes the prodomain and the metalloprotease domain.These transgenes are driven by the mouse muscle creatine kinase (MCK) promoter for the muscle-specific expression.One, two and three transgenic founders were obtained for each of transgenes C3, TRC and MP, respectively. Transgenic individuals were fertile and transmitted the bovine ADAM12 genes to the offsprings.All transgenic lines did not differ from littermate controls in body weight and fat content. However, TRC and MP transgenic mice developed the increased intramuscular fat deposition more than littermate controls, but C3 transgenic mice did not.The observation of similar phenotypes between TRC and MP transgenic mice muscle tissues suggested that ADAM12 metalloprotease domain was sufficient to induce the intramuscular fat deposition.

ADAM 12是ADAM（一种去整合素和金属蛋白酶）家族的成员，并且最近被认为在调节肌生成和脂肪生成中起作用。也有报道在肌肉组织中特异性表达人ADAM 12的转基因小鼠表现出肌内脂肪沉积。由于这些表型与牛肉大理石花纹相似，本研究利用转基因技术制备了肌肉组织特异性表达牛ADAM 12基因的转基因小鼠，建立了大理石花纹动物模型。MCK-bADAM 12 C3编码一种膜锚定的ADAM 12蛋白，由前结构域、金属蛋白酶、去整合素、富含半胱氨酸和跨膜结构域以及胞质尾组成。MCK-bADAM 12 TRC编码由整个胞外结构域组成的分泌型蛋白。MCK-bADAM 12 MP基因编码前结构域和金属蛋白酶结构域，由小鼠肌肉肌酸激酶（MCK）启动子驱动，在肌肉特异性表达，C3、TRC和MP分别获得1、2和3个转基因建立者。转基因个体具有生育能力，并将牛的ADAM 12基因传递给后代，所有转基因品系的体重和脂肪含量与同窝对照没有差异。TRC和MP转基因小鼠肌内脂肪沉积明显增加，而C3转基因小鼠肌内脂肪沉积明显增加，TRC和MP转基因小鼠肌内脂肪沉积表型相似，提示ADAM 12金属蛋白酶结构域足以诱导肌内脂肪沉积。

项目成果

Future of Studies on Beef Marbling : From Identification of Responsible Genes To Understanding of Gene Network

牛肉大理石花纹研究的未来：从责任基因的识别到基因网络的理解

• 发表时间: 2006
• 期刊: The Journal of Animal Genetics 34-2
• 作者: Bah MM;Acosta TJ;Pilawski W;Deptula K;Okuda K;Skarzynski DJ;Tatsukawa Y;Miyamoto A;山下 淳;Jun Yamashita;山下 淳;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;山下 淳;山下 淳;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Jun Yamashita;Jun Yamashita;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;山下 淳;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Jun Yamashita;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;谷口幸雄;Yukio TANIGUCHI
• 通讯作者: Yukio TANIGUCHI

ウシ脂肪交雑研究の今後 : 責任遺伝子の同定から形成機構の解明へ

牛大理石花纹研究的未来：从识别相关基因到阐明形成机制

• 发表时间: 2006
• 期刊: 動物遺伝育種研究 34・2
• 作者: Bah MM;Acosta TJ;Pilawski W;Deptula K;Okuda K;Skarzynski DJ;Tatsukawa Y;Miyamoto A;山下 淳;Jun Yamashita;山下 淳;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;山下 淳;山下 淳;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Jun Yamashita;Jun Yamashita;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;山下 淳;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;Jun Yamashita;Shaikh Tanveer Hossain;Shaikh Tanveer Hossain;谷口幸雄
• 通讯作者: 谷口幸雄