Animal model of brain tumor and manufacturing method of animal model

Patent metadata

Field	Value
Publication number	US-11490603-B2
Application number	US-201816050006-A
Country	US
Kind code	B2
Filing date	Jul 31, 2018
Priority date	Feb 6, 2018
Publication date	Nov 8, 2022
Grant date	Nov 8, 2022

Abstract

The present invention relates to a brain tumor animal model that directly reflects the phenomenon in a human patient and a method of preparing the same, and more specifically, a brain tumor animal model that mutations are introduced into p53, Pten, and EGFR genes, a screening method of a therapeutic agent for a brain tumor using the animal model, and a preparing method thereof.

First claim

The invention claimed is:

1. A transgenic mouse comprising, knock-out mutations of p53 and Pten genes specifically in nerve stem cells of subventricular zone (SVZ), and
an activating mutation of epidermal growth factor receptor VIII (EGFRviii) gene in nerve stem cells of SVZ,
wherein a glioblastoma occurs in the dorsolateral-caudal cortex region,
wherein the glioblastoma develops from nerve stem cells that are positive for Glial fibrillary acidic protein (GFAP),
wherein the GFAP positive nerve stem cells have normal cytoarchitecture.

2. The transgenic mouse of claim 1 , wherein the glioblastoma is a high-grade glioblastoma having characteristics of necrosis, microvascular proliferation and mitosis, and has an immune response to GFAP, Nestin, Olig2, and PDGFRα.

3. The transgenic mouse of claim 1 , wherein the mouse maintains the knockout mutation of p53 and Pten gene specific to nerve stem cells in SVZ even after glioblastoma occurrence.

4. The transgenic mouse of claim 1 , wherein the p53 gene comprise at least a nucleotide sequence of SEQ. ID NOs. 38 to 40, and the Pten gene comprise at least a nucleotide sequence of SEQ. ID NOs. 41 to 43.

Assignees

• Korea Advanced Inst Sci & Tech
• Yonsei Univ Univ—Industry Foundation Uif

Inventors

• Kang Seok Gu
• Lee Jeong Ho
• Lee Joo Ho
• Lee Jeong Eun

Classifications

• C12Q1/6881 Primary

  for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title

• A01K67/0276 Primary

  Knock-out vertebrates · CPC title

• A01K2217/075

  inducing loss of function, i.e. knock out · CPC title

• C07K16/40

  against enzymes · CPC title