Diagnosis marker, diagnosis method and therapeutic agent for amyotrophic lateral sclerosis, and animal model and cell model developing amyotrophic lateral sclerosis

Abstract

Provided are a diagnosis marker, a diagnosis method, and a therapeutic agent suitable for diagnosing and treating amyotrophic lateral sclerosis (ALS). Also provided are an animal model and a cell model suitable for developing a therapeutic agent and a treatment method for ALS. The diagnosis method for ALS includes: an isolation step in which a nucleic acid is isolated from a specimen taken from a subject; a detection step in which bases expressed in a human chromosome 10 optineurin (OPTN) gene region are detected from the isolated nucleic acid; and a determination step in which it is determined whether or not the detected bases are mutated.

1 . A diagnosis marker for amyotrophic lateral sclerosis, containing a nucleic acid composed of a base sequence having a mutation in human chromosome 10 OPTN (Optineurin) gene regions. 
     
     
         2 . The diagnosis marker for amyotrophic lateral sclerosis of  claim 1 , wherein out of the OPTN gene regions, the bases indicated by the 13207995 region and/or the 13214104 region are mutated bases. 
     
     
         3 . The diagnosis marker for amyotrophic lateral sclerosis of  claim 2 , wherein the base in the 13207995 region has mutated from cytosine to thymine, or the base in the 13214104 region has mutated from adenine to guanine. 
     
     
         4 . A diagnosis method for amyotrophic lateral sclerosis, comprising:
 an isolation step in which a sample is taken from a subject and a nucleic acid is isolated from this sample;   a detection step in which bases expressed in human chromosome 10 OPTN (Optineurin) gene regions are detected from the isolated nucleic acid; and   a determination step in which it is determined whether or not the detected bases are mutated.   
     
     
         5 . The diagnosis method for amyotrophic lateral sclerosis of  claim 4 , wherein in the determination step, a determination is made as to whether the base in the 13207995 region has mutated from cytosine to thymine, or whether the base in the 13214104 region has mutated from adenine to guanine, out of the OPTN gene regions. 
     
     
         6 . A therapeutic agent for amyotrophic lateral sclerosis wherein when bases expressed in a human chromosome 10 OPTN (Optineurin) gene region have mutated, read-through of these bases is induced. 
     
     
         7 . The therapeutic agent for amyotrophic lateral sclerosis of  claim 6 , wherein out of the OPTN gene regions, read-through of the base expressed in the 13207995 region is induced. 
     
     
         8 . A therapeutic agent for amyotrophic lateral sclerosis wherein activation of the NF-κB transcription factor is inhibited. 
     
     
         9 . A therapeutic agent for amyotrophic lateral sclerosis wherein localization of OPTN coded by a human chromosome 10 OPTN (Optineurin) gene in the cell is made suitable, and/or the loss of function achieved by this localization is compensated for. 
     
     
         10 . The therapeutic agent for amyotrophic lateral sclerosis of  claim 9 , wherein the therapeutic agent functions to the Golgi body in the cell. 
     
     
         11 . An animal model for outbreaks of amyotrophic lateral sclerosis in which a DNA fragment containing mutated bases in the bases indicated in a human chromosome 10 OPTN (Optineurin) gene region, and/or an expression vector, are introduced. 
     
     
         12 . A cell model for outbreaks of amyotrophic lateral sclerosis, sampled from the animal model of  claim 11 .