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Establishment method and application of CCM3 knockout mouse model

A gene knockout mouse and method establishment technology, applied in the field of biomedicine, can solve the problems of unavailable CCM pathogenesis and treatment methods, embryonic lethality, etc.

Inactive Publication Date: 2016-12-07
广州道瑞医药科技有限公司
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Problems solved by technology

CCM1, CCM2, and CCM3 are currently discovered CCM pathogenic genes, but mice with endothelial cell-specific knockout of CCM1, CCM2, and CCM3 often lead to embryonic lethality due to abnormal vascular development, and cannot be used for the pathogenesis and treatment methods or drugs of CCM Research

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  • Establishment method and application of CCM3 knockout mouse model
  • Establishment method and application of CCM3 knockout mouse model
  • Establishment method and application of CCM3 knockout mouse model

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Embodiment Construction

[0017] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific examples. Methods that are not described in detail in the examples can be implemented by conventional experimental methods.

[0018] Tamoxifen (tamoxifen), that is, tamoxifen; Ccm3 and CCM3 can be used interchangeably; Cdh5-CreERT2 transgenic mice and tamoxifen-induced Cdh5CreERT2 knockout mice can be used interchangeably; Px day is the xth day sky.

[0019] 1. Materials and methods

[0020] 1.1 Tamoxifen-induced vascular endothelial cell-specific Ccm3 knockout mouse (Ccm3-iecKO) model

[0021] To facilitate the study of the function of Ccm3 in vascular endothelial cells via the Cre-LoxP system, we used Cdh5-CreERT2 transgenic mice. The principle of Cdh5-CreERT2 transgenic technology is to firstly mutate the ligand-binding domain (LBD) of estrogen receptor (ER), and then fuse it wi...

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Abstract

The invention discloses an establishment method of a CCM3 knockout mouse model. The method comprises the steps that the tamoxifen induced CCM3 knockout mouse model with vascular endothelial cell specificity is obtained by mating a CCM3lox / lox mouse and a tamoxifen induced Cdh5CreERT2 knockout mouse. The mouse model has the pathological characteristics of human brain cavernous malformation after being induced by tamoxifen, is very suitable for human brain cavernous malformation pathogenesis study and development of corresponding treatment medicine and treatment methods, and can also be used for observing and evaluating the medicine effect of the medicine.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a method for establishing a CCM3 gene knockout mouse model and an application thereof. Background technique [0002] Cerebral cavernous malformation (cerebral carvernoμs malformation, CCM) is a kind of vascular malformation that occurs in the central nervous system. The disease rate is about 0.1% to 4%. CCM, purplish red in appearance, spongy or honeycomb-shaped in section, is composed of irregular vascular cavities of various sizes gathered into a spongy abnormal vascular mass, with a lumen ranging from 1 to 10 mm, and a layer of flat endothelial cells on the inner wall. There is no nerve tissue between the vascular spaces, only a small amount of connective tissue. Under the naked eye, CCM is a mass of thin-walled vascular lumens, mulberry-shaped, with clear boundaries, and hemosiderosis can be seen. Under the microscope, it can be seen that it is composed of ...

Claims

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Application Information

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IPC IPC(8): A01K67/02A61K31/138A61K49/00
CPCA01K67/02A61K31/138A61K49/0008
Inventor 王敏周焕娇
Owner 广州道瑞医药科技有限公司
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