An invertebrate animal model with neurodegenerative phenotype for screening and testing substances

Abstract

The present invention claims an invertebrate animal that has been modified to express a set of genes, said set comprising the gene coding for a modified version of the gamma subunit of AMP-activated protein kinase (AMPKg). According to the invention, the animal displays an identifiable phenotype related to lipid metabolism and neurodegeneration. This animal provides a model of neurodegenerative diseases, particularly Alzheimer's disease, and may be useful for screening and testing modulating agents, substances and therapeutic compounds for neurodegenerative disorders.

1 . A non-human animal that expresses a modified version of the gene coding for the gamma subunit of AMP-activated protein kinase (AMPKg).  
     
     
         2 . The animal according to  claim 1 , wherein said animal is an invertebrate.  
     
     
         3 . The animal according to  claim 2 , wherein said animal is an insect, preferably a fly.  
     
     
         4 . The animal according to  claim 1 , obtainable by a method selected from the group consisting of transposon insertion mutagenesis and chemical mutagenesis of the gene coding for the gamma subunit of AMP-activated protein kinase (AMPKg).  
     
     
         5 . The animal according to  claim 1 , wherein said modified version of the gene coding for the gamma subunit of AMP-activated protein kinase (AMPKg) is the loechrig (loe) mutation.  
     
     
         6 . The animal according to  claim 1 , wherein the expression of said gene results in an identifiable phenotype.  
     
     
         7 . The animal according to  claim 6 , wherein said identifiable phenotype is related to lipid metabolism and/or is a neurodegenerative phenotype.  
     
     
         8 . The animal according to  claim 1 , wherein said animal expresses a gene coding for an amyloid precursor protein, or a modified version thereof, in particular a fragment or a mutant thereof.  
     
     
         9 . The animal according to  claim 8 , wherein said modified version of the gene coding for an amyloid precursor protein is a modified version of the gene coding for beta amyloid protein precursor-like (Appl) protein.  
     
     
         10 . The animal according to  claim 8 , wherein said modified version comprises a deletion, or a partial deletion, of the gene coding for beta amyloid protein precursor-like (Appl) protein, wherein said deletion, or partial deletion results in a loss-of-function of said gene.  
     
     
         11 . The animal according to  claim 1 , wherein said animal is transgenic for a modified version of the gene coding for the gamma subunit of AMP-activated protein kinase (AMPKg) and/or a gene coding for an amyloid precursor protein, or a modified version thereof, in particular a fragment or a mutant thereof.  
     
     
         12 . Use of an animal according to  claim 1  for identifying a modulator which affects lipid metabolism.  
     
     
         13 . Use of an animal according to  claim 1  for identifying a modulator which affects a neurodegenerative phenotype.  
     
     
         14 . Use of an animal according to  claim 1  for identifying a modulator which affects processing of an amyloid precursor protein.  
     
     
         15 . A method of identifying a modulator according to  claim 12 , comprising administering a substance, or a plurality of substances, to said animal; and observing the effect of said substance, or plurality of substances, on said animal.  
     
     
         16 . The method according to  claim 15 , wherein said substance, or plurality of substances, is orally administered to said animal.  
     
     
         17 . Use of an animal according to  claim 1  for identifying whether a gene, or a mutant thereof, is capable of modulating a phenotype related to lipid metabolism and/or neurodegeneration, in particular processing of an amyloid precursor protein.