Non-mammalian transgenic animal having an adult onset neurodegenerative phenotype

Abstract

Transgenic non-mammalian animals, e.g. flies, that exhibit an adult onset neurodegenerative phenotype, as well as methods for preparing the same, are provided. Also provided are methods of using the subject transgenic non-mammalian animals to identify compounds having activity with respect to adult onset neurodegenerative diseases. Finally, kits for screening compounds for anti-neurodegenerative activity are provided.

What is claimed is:  
     
         1 . A non-mammalian animal that exhibits an adult onset neurodegenerative phenotype, wherein said phenotype results from a non-adult expression mutation.  
     
     
         2 . The non-mammalian animal according to  claim 1 , wherein said animal is a transgenic non-mammalian animal comprising a transgene that is expressed in the non-adult animal and gives rise to said phenotype.  
     
     
         3 . The transgenic non-mammalian animal according to  claim 2 , wherein said transgenic non-mammalian animal is an invertebrate.  
     
     
         4 . The transgenic non-mammalian animal according to  claim 3 , wherein said invertebrate is an insect.  
     
     
         5 . A transgenic fly that exhibits an adult onset neurodegenerative phenotype, wherein said phenotype results from a non-adult expressed transgene.  
     
     
         6 . The transgenic fly according to  claim 5 , wherein said transgene is expressed during the embryonic developmental stage of said fly.  
     
     
         7 . The transgenic fly according to  claim 6;  wherein said transgene is expressed in embryonic neuroblasts of said fly.  
     
     
         8 . The transgenic fly according to  claim 5 , wherein said transgene is a myb gene.  
     
     
         9 . The transgenic fly according to  claim 8 , wherein said myb gene expresses a protein that is capable of binding to DNA and activating transcription.  
     
     
         10 . A transgenic Drosophila melanogaster that exhibits an adult onset neurodegenerative phenotype, wherein said transgenic Drosophila melanogaster comprises a myb transgene that is expressed in embryonic neuroblasts.  
     
     
         11 . The transgenic Drosophila melanogaster according to  claim 10 , wherein said myb gene encodes a product that binds to DNA and is capable of activating transcription.  
     
     
         12 . The transgenic Drosophila melanogaster according to  claim 10 , wherein said myb gene is a chicken or viral myb gene.  
     
     
         13 . A method of screening a compound for activity with respect to an adult onset neurodegenerative disease, said method comprising: 
 administering said compound to a non-mammalian animal according to  claim 1;  and    observing the effect of said compound on said animal.    
     
     
         14 . The method according to  claim 13 , wherein said non-mammalian animal is a transgenic invertebrate.  
     
     
         15 . The method according to  claim 14 , wherein said invertebrate is an insect.  
     
     
         16 . The method according to  claim 15 , wherein said insect is a fly.  
     
     
         17 . The method according to  claim 13 , wherein said compound is orally administered to said animal.  
     
     
         18 . A method of screening a compound for activity with respect to an adult onset neurodegenerative disease, said method comprising: 
 feeding said compound to a non-mammalian animal according to  claim 1;  and    observing the effect of said compound on said animal.    
     
     
         19 . The method according to  claim 18 , wherein said compound is present in a nutrient medium.  
     
     
         20 . A method of screening a plurality of compounds for activity with respect to an adult onset neurodegenerative disease, said method comprising: 
 feeding said plurality of compounds to a plurality of non-mammalian animals according to  claim 1  in a manner sufficient to ensure that each animal is fed only a single type compound from said plurality of compounds; and    observing the effect of said compounds on said plurality of animals.    
     
     
         21 . The method according to  claim 20 , wherein said compound is present in a nutrient medium.  
     
     
         22 . A method of identifying whether a gene is capable of modulating an adult onset neurodegenerative condition, said method comprising: 
 mutating said gene in a non-mammalian animal according to  claim 1;  and    determining whether said mutation modulates the phenotype of said non-mammalian animal model.    
     
     
         23 . The method according to  claim 22 , wherein said modulating is enhancing.  
     
     
         24 . The method according to  claim 22 , wherein said modulating is suppressing.  
     
     
         25 . A method of treating a host suffering from a neurodegenerative disease, said method comprising: 
 administering to said host a compound that modulates the expression of a gene identified according to the method of  claim 22 .    
     
     
         26 . A kit for use in screening compounds for activity with respect to an adult onset neurodegenerative disease, said kit comprising: 
 a non-mammalian animal according to  claim 1  or a precursor thereof.    
     
     
         27 . The kit according to  claim 26 , wherein said kit further comprises a nutrient medium for said animal.  
     
     
         28 . A compound having activity with respect to an adult onset neurodegenerative disease, said compound identified according to the method of  claim 18 .  
     
     
         29 . The compound according to  claim 28 , wherein said compound is present in a pharmaceutical composition.  
     
     
         30 . A method of treating a host suffering from a neurodegenerative disease, said method comprising: 
 administering an effective amount of a compound according to  claim 28  to said host.    
     
     
         31 . A Drosophila melanogaster regulatory element that activates gene expression in embryonic neuroblasts.  
     
     
         32 . The regulatory element according to  claim 27 , wherein said regulatory element is located at 86E1-3.  
     
     
         33 . A method for validating a non-mammalian animal model of a human disease condition, said method comprising: 
 administering a compound known to have activity against said human disease to a potential non-mammalian animal model for said disease, wherein said potential non-mammalian animal model has a phenotype that is analogous to said human disease phenotype; and    determining whether said compound has the same effect on said non-mammalian animal phenotype as it does on said human disease phenotype.    
     
     
         34 . A transgenic non-mammalian animal, wherein said animal comprises a myb transgene that is expressed in embryonic neuroblasts.