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CSF1R gene humanized non-human animal and construction method and application thereof

A non-human animal and construction method technology, applied in chemical instruments and methods, botany equipment and methods, biochemical equipment and methods, etc., can solve the problem that animal models cannot reflect the real situation of the human body well

Pending Publication Date: 2021-06-29
BIOCYTOGEN JIANGSU CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the differences in the physiological structure and metabolic system between animals and humans, traditional animal models cannot well reflect the real conditions of the human body. It is an urgent need for the biomedical industry to establish disease models in animals that are closer to the physiological characteristics of humans

Method used

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  • CSF1R gene humanized non-human animal and construction method and application thereof
  • CSF1R gene humanized non-human animal and construction method and application thereof
  • CSF1R gene humanized non-human animal and construction method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0200] Embodiment 1 CSF1R gene humanized mouse

[0201]In this example, a non-human animal (such as a mouse) is transformed so that the non-human animal contains all or part of the nucleotide sequence encoding human CSF1R protein, so as to obtain a genetically modified non-human animal that can express human or Humanized CSF1R protein. Mouse CSF1R gene (NCBI Gene ID: 12978, Primary source: MGI: 1339758, UniProt ID: P09581, located at positions 61105572 to 61131139 of chromosome 18 NC_000084.6, based on transcript NM_001037859.2 (SEQ ID NO: 1) Its encoded protein NP_001032948.2 (SEQ ID NO: 2)) and human CSF1R gene (NCBI Gene ID: 1436, Primary source: HGNC: 2433, UniProt ID: P07333, located at No. 150053291 to 150113372 of chromosome 5 NC_000005.10 position, based on the comparison of the transcript NM_001288705.3 (SEQ ID NO: 3) and its encoded protein NP_001275634.1 (SEQ ID NO: 4)) as shown in figure 1 shown.

[0202] In order to achieve the purpose of the present invention,...

Embodiment 2

[0228] Embodiment 2 Preparation of double humanized or multiple humanized mice

[0229]Double-humanized or multiple-humanized mouse models can also be prepared by using the method or the prepared CSF1R mice. For example, in the aforementioned Example 1, embryonic stem cells used in blastocyst microinjection can be selected from mice containing other genetic modifications such as PD-1, PD-L1, CSF1, IL34, CCR2, CD40, CXCR4, VEGF, and PDGF Alternatively, on the basis of humanized CSF1R mice, mouse ES cells can be isolated and gene recombination targeting technology can be used to obtain CSF1R and other genetically modified double-gene or multi-gene modified mouse models. The homozygous or heterozygous CSF1R mice obtained by this method can also be mated with other genetically modified homozygous or heterozygous mice, and their offspring can be screened. According to the Mendelian law of inheritance, there is a certain probability of obtaining humanized CSF1R Heterozygous mice wi...

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Abstract

The invention provides a CSF1R gene humanized non-human animal as well as a construction method and application thereof in the field of biomedicines. The construction method comprises: introducing all or part of a nucleotide sequence of the human CSF1R gene into genome of a non-human animal by homologous recombination, so that the animal can normally express human or humanized CSF1R protein in vivo. The non-human animal can be used as an animal model for human CSF1R signal mechanism research and tumor and immune disease drug screening, and has important application value for new drug research and development of immune targets. The invention also provides a humanized CSF1R protein, a humanized CSF1R gene and a targeting vector of the CSF1R gene.

Description

technical field [0001] The invention belongs to the field of animal genetic engineering and genetic modification, and in particular relates to a CSF1R gene humanized non-human animal, its construction method and its application in the field of biomedicine. Background technique [0002] Experimental animal disease models are indispensable research tools for the study of the etiology and pathogenesis of human diseases, the development of prevention technologies and the development of drugs. However, due to the differences in the physiological structure and metabolic system between animals and humans, traditional animal models cannot well reflect the real conditions of the human body. It is an urgent need for the biomedical industry to establish disease models in animals that are closer to the physiological characteristics of humans . [0003] With the continuous development and maturity of genetic engineering technology, the replacement or replacement of homologous genes in a...

Claims

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Application Information

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IPC IPC(8): C12N15/85A01K67/027C07K14/715C12N15/12C12N5/10A61K49/00
CPCC12N15/8509C07K14/715A01K67/0278A61K49/0008C12N2800/107A01K2227/105A01K2267/0331A01K2267/0387A01K2267/0368
Inventor 沈月雷郭朝设张美玲黄蕤白阳周小飞
Owner BIOCYTOGEN JIANGSU CO LTD
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