Ganglioglioma-induced animal model and a method for diagnosing and treating ganglioglioma and related diseases

Patent metadata

Field	Value
Publication number	US-12364776-B2
Application number	US-201816486905-A
Country	US
Kind code	B2
Filing date	Jun 26, 2018
Priority date	Jun 29, 2017
Publication date	Jul 22, 2025
Grant date	Jul 22, 2025

Abstract

The present invention relates to a biomarker of epilepsy, a composition for diagnosing epilepsy, an epilepsy-induced animal, and a composition for preventing or treating epilepsy, and specifically, relates to a composition for diagnosing epilepsy comprising a BRAF mutant protein and a nucleic acid molecule, and an agent capable of detecting the protein or nucleic acid molecule, an epilepsy-induced animal transformed with the BRAF mutant nucleic acid molecule, and a composition for prevention or treatment of epilepsy comprising a BRAF mutant protein activity inhibitor.

First claim

The invention claimed is:

1. A murine model with ganglioglioma or epilepsy caused by ganglioglioma, wherein the animal model is prepared by obtaining an embryo from a conditional mutant transgenic animal including a nucleic acid molecule encoding a BRAF mutant protein and inducing expression of the BRAF mutant protein or the nucleic acid molecule encoding the BRAF mutant protein in neural progenitor cells of lateral ventricle of the embryo at embryonic day 14 (E14), wherein the BRAF mutant protein consisting of an amino acid sequence comprising a mutation in which valine at position 600 is substituted to glutamic acid in an amino acid sequence of SEQ ID NO: 1, or a BRAF mutant protein consisting of an amino acid sequence comprising a mutation in which valine at position 637 is substituted to glutamic acid in an amino acid sequence of SEQ ID NO: 3, and wherein the animal model has characteristics of activated MARK signaling pathway of Ras-Raf-MEK-ERK, dysplasia of nerve cells, and malformation of cortical development.

2. The murine model according to claim 1 , wherein the animal has a spontaneous seizure.

3. The murine model according to the claim 1 , wherein the mutant nucleic acid molecule comprises a mutation in which thymine at position 1799 is substituted to adenine in the nucleotide sequence of SEQ ID NO: 2, or thymine at position 1910 is substituted to adenine in the nucleotide sequence of SEQ ID NO: 4.

4. The murine model according to the claim 1 , wherein the ganglioglioma or epilepsy caused by ganglioglioma is not caused by activation of the mTOR signaling pathway.

5. The murine model according to claim 1 , wherein the animal model expresses the BRAF mutant protein in nerve cells and glial cells of brain.

Assignees

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

Inventors

• Lee Jeong Ho
• Koh Hyun Yong
• Kim Dong Seok

Classifications

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title