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Construction method and application of il17rb gene humanized non-human animal

A non-human animal and construction method technology, applied in the field of construction of IL17RB genetically modified non-human animal models

Active Publication Date: 2021-06-04
BIOCYTOGEN PHARMACEUTICALS (BEIJING) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Therefore, due to the differences in physiology and pathology between animals and humans, and the complexity of the IL17RB gene, how to construct an "effective" IL17RB humanized animal model for new drug development is still the biggest challenge

Method used

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  • Construction method and application of il17rb gene humanized non-human animal
  • Construction method and application of il17rb gene humanized non-human animal
  • Construction method and application of il17rb gene humanized non-human animal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0129] Example 1 IL17RB Gene Humanized Mice

[0130] Mouse IL17RB gene (NCBI Gene ID: 50905, Primary source: MGI: 1355292, UniProt: Q9JIP3, located at positions 29718125 to 29730853 of chromosome 14 NC_000080.7, based on the transcript NM_019583.3 and its encoded protein NP_062529.2 ( SEQ ID NO: 1)) and human IL17RB gene (NCBI Gene ID: 55540, Primary source: HGNC: 18015, UniProt ID: Q9NRM6, located at positions 53846550 to 53867388 of chromosome 3 NC_000003.12, based on transcript NM_018725.4 and its encoded protein NP_061195.2 (SEQ IDNO: 2)) comparison diagram as shown figure 1 shown.

[0131] In order to achieve the purpose of the present invention, a nucleotide sequence encoding human IL17RB protein can be introduced into the mouse endogenous IL17RB locus, so that the mouse expresses human or humanized IL17RB protein. Specifically, using gene editing technology, under the control of mouse IL17RB gene regulatory elements, the partial sequence of exon 2 to exon 10 of human ...

Embodiment 2

[0165] Example 2 Preparation of double humanized or multiple double humanized mice

[0166] Double-humanized or multiple-humanized mouse models can also be prepared by using the method or the prepared IL17RB mice. For example, in the aforementioned Example 1, the embryonic stem cells used for blastocyst microinjection can be selected from mice containing other genetic modifications such as PD-1, PD-L1, IL17A, IL17F, IL17RA, and IL17RC, or can also be used in On the basis of humanized IL17RB mice, using the isolation of mouse ES embryonic stem cells and gene recombination targeting technology, a mouse model of IL17RB and other genetic modifications with double genes or multiple genes is obtained. The homozygous or heterozygous IL17RB 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 Mendelian inheritance, there is a certain probability of obtaining humanized IL17RB H...

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Abstract

The present invention provides a method for constructing IL17RB gene humanized non-human animals, which uses homologous recombination to introduce the nucleotide sequence encoding human IL17RB protein into the non-human animal genome, and the animal can normally express human The IL17RB protein can be used as an animal model for human IL17RB signaling mechanism research, tumor and immune disease drug screening, and has important application value for the development of new drugs for immune targets. The present invention also provides a humanized IL17RB protein, a humanized IL17RB gene, a targeting vector for the IL17RB gene, and the non-human animal obtained by the above construction method and its application in the field of biomedicine.

Description

technical field [0001] The invention belongs to the field of animal genetic engineering and genetic modification, and in particular relates to a method for constructing an IL17RB genetically modified non-human animal model and its application in the field of biomedicine. Background technique [0002] Interleukin (IL) 17 cytokines (IL17 for short) family is a kind of characteristic cytokines, which are mainly secreted by activated Th17 cells. Six members of the IL17 family have been discovered, namely IL17A, IL17B, IL17C, IL17D, IL17E and IL17F. The IL17 receptor (IL17R for short) also forms a unique family, and five homologous subunits have been discovered so far, namely IL17RA, IL17RB, IL17RC, IL17RD, and IL17RE. IL17 binds to receptors, activates its downstream signaling pathways (including MAP kinase pathway, NF-kB pathway, mRNA stabilization signaling pathway, ERK signaling pathway, and JAK / STAT signaling pathway, etc.), and stimulates a variety of cells to produce infl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/85C12N15/12A01K67/027
CPCA01K67/0278A01K2217/072A01K2227/105A01K2267/03C07K14/7155C12N15/8509
Inventor 赵磊刘畅
Owner BIOCYTOGEN PHARMACEUTICALS (BEIJING) CO LTD