Genetically-modified non-human animal and application thereof

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...

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 ineffective in mouse plasma, in summary, such a genetically modified Animals, such as mice, are impossible to generate

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