Genetically-modified non-human animal and application thereof

A genetically modified, non-human technology, applied to genetically modified non-human animals and their application fields, can solve the problem that human protein C cannot function effectively.

Active Publication Date: 2020-06-19
SHANGHAI RAAS BLOOD PRODUCTS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since mice lacking protein C (i.e., protein C-null mice) are born dead, and human protein C is reported to be

Method used

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  • Genetically-modified non-human animal and application thereof
  • Genetically-modified non-human animal and application thereof
  • Genetically-modified non-human animal and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0228] Constructive knock-in mouse model of human protein C

[0229] Targeting carrier

[0230] A targeting vector for knocking the human protein C gene into the mouse (C57BL / 6) protein C gene location was constructed. The nucleotide sequence of the targeting vector is set forth in SEQ ID NO:1.

[0231] The mouse protein C gene (NCBI reference sequence: NM_001042767.3) is located on mouse chromosome 18. Nine exons have been identified, of which the ATG of exon 2 is the start codon and the TAG of exon 9 is the stop codon.

[0232] Human protein C gene (NCBI reference sequence: NM_000312.3) is located on human chromosome 2. Nine exons have been identified, of which the ATG of exon 2 is the start codon and the TAG of exon 9 is the stop codon.

[0233]For the knock-in model mice described herein, the region from the ATG start codon to the TAG stop codon of mouse protein C was replaced with the coding sequence of human protein C. Thus, the targeting vector includes the...

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PUM

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Abstract

The invention relates to a genetically-modified non-human animal and application thereof, in particular to a transgenic mouse model and application thereof in the aspect of screening of a targeted medicine. According to the transgenic mouse model and application thereof in the aspect of screening of the targeted medicine, by targetedly knocking out and replacing a mouse protein C gene by means ofa human protein C gene expression cassette, a humanized protein C knock-in mouse is generated. The mouse has fertility, and can hybridize with another mouse disease model (such as a mouse in the deficiency of a blood coagulation factor VIII or a blood coagulation factor IX) to produce a humanized protein C mouse disease model (such as a humanized protein C factor VIII-deficient mouse model or a humanized protein C factor IX-deficient mouse model). The mouse model can be used for studying functions in vivo of human protein C and human activated protein C (APC). The mouse model is the first mouse model used for testing a therapeutic candidate medicine, which targets the human protein C or the APC, in vivo, and has very high economic value and scientific research value.

Description

technical field [0001] The invention relates to a transgenic mouse model and its application in screening targeted drugs. These mouse models are the first mouse models for in vivo testing of therapeutic drug candidates targeting human protein C or APC, and have high economic and scientific value. Background technique [0002] The genetic modification of non-human animals involved in the present invention is to replace the nucleotide sequence encoding a certain endogenous protein in the genome of the original animal with a homologous human nucleotide sequence. Also provided are vectors, cells and methods for producing such non-human animals. The present invention also provides a method for detecting the expression and / or functional activity of the human protein in non-human animals, thereby laying the foundation for its pharmacodynamic research. [0003] The human protein C pathway plays a key role in regulating coagulation and inflammatory responses. Activation of human p...

Claims

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Application Information

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IPC IPC(8): A01K67/027C12N5/10C12N15/85C12N15/90A61K49/00
CPCA01K67/0278A01K67/0276C12N9/6464C12N9/644C07K14/755C12N5/0606C12N15/8509C12N15/907A61K49/0008C12Y304/21069C12Y304/21022A01K2207/15A01K2217/072A01K2227/105A01K2217/075A01K2267/0368A01K2267/0381C12N2510/00C12N2800/107
Inventor 徐俊程露刘业恒易佳炜周雪峰
Owner SHANGHAI RAAS BLOOD PRODUCTS CO LTD
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