Non-mammalian transgenic animal having an adult onset neurodegenerative phenotype

a non-mammalian, neurodegenerative technology, applied in the field of transgenic flies, can solve the problems of difficult use, no cure, limited treatment of such diseases,

Inactive Publication Date: 2003-02-13
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0031] As mentioned above, the subject transgenic flies find particular utility in screening assays designed to identify therapeutic compounds for neurodegenerative conditions, particularly adult onset neurodegenerative conditions. Through use of the subject transgenic flies (or cells derived therefrom depending on the particular screening assay), one can identify compounds that have activity with respect to an adult onset neurodegenerative disease. Compounds have activity with respect to an adult onset neurodegenerative disease if they modulate or have an effect on at least one parameter or symptom of the disease, such as loss of appetite, loss of motor coordination, etc., where the modulatory activity may be to reduce or enhance the magnitude of the symptom. Thus, the screening methods of subject invention can be used to identify compounds that modulate the progression of neurodegenerative disease, e.g. by binding to, modulating, enhancing or repressing the activity of a protein or peptide involved in the progression of the neurodegenerative disease, and / or compounds that ameliorate, alleviate or even remove the phenotypic symptoms of the disease, where such activity may or may not be the result of activity with respect to the underlying mechanism of the disease. Screening to determine drugs that lack effect on the neurodegeneration condition is also of interest. Assays of the invention make it possible to identify compounds which ultimately: (1) have a positive affect with respect to a neurodegenerative disease condition and as such are therapeutics, e.g. agents which arrest or reverse the neurodegeneration or ameliorate or alleviate the symptoms of such a condition; or (2) have an adverse affect with respect to the neurodegeneration disease and as such should be avoided as therapeutic agents.

Problems solved by technology

Currently, treatment of such diseases is limited to disease management and there are no cures.
However primates are expensive, difficult to use, and require a significant period of time prior to developing adult onset neurodegenerative symptoms.
These factors make the use of primates as adult onset neurodegenerative animal models prohibitive.
Transgenic mice suffer from analogous disadvantages, i.e. expense, slow reproduction time, and generation of small numbers of offspring.

Method used

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Embodiment Construction

[0014] Non-mammalian transgenic animals, particularly insects, e.g. flies, that exhibit adult onset neurodegeneration, as well as methods for their preparation, are provided. The subject transgenic animals are further characterized in that they comprise a stably integrated transgene which is expressed in embryonic neuroblasts, where the expressed product results in the observed adult onset neurodegenerative phenotype. In preferred embodiments, the transgene is a myb gene. Also provided are methods of using the subject non-mammalian transgenic animals to screen for compounds having activity with respect to adult onset neurodegeneration, particularly compounds that are therapeutic for neurodegenerative diseases. In further describing the subject invention, the transgenic animals and methods for their production will be detailed first, followed by a discussion of the screening methods of the subject invention.

Animal Models

[0015] In the broadest sense, the invention provides non-mammali...

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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.

Description

[0001] This patent application is a continuation of U.S. Patent Application No. 09 / 472,663, filed Dec. 27, 1999 which claims priority to the filing date of the United States Provisional Patent Application Serial No. 60 / 148,404 filed Aug. 11, 1999 and United States Provisional Patent Application Serial No. 60 / 125,586 filed Mar. 18, 1999; the disclosures of which are herein incorporated by reference.[0003] 1. Field of the Invention[0004] The field of this invention is transgenic flies.[0005] 2. Background of the Invention[0006] Adult onset neurodegenerative diseases are among some of the most devastating diseases currently afflicting mankind, at least in the developed nations of the world. Such diseases "are characterized by onset in adult life, chronic progressive course, distinct clinical phenotypes, specific cellular abnormalities involving subsets of neurons, and eventually fatal outcomes." Price et al., Science (Nov. 6, 1998) 282: 1079-1083. Examples of neurodegenerative diseases...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A01K67/027A01K67/033A61K45/00A61P25/28C07K14/47C12N15/85G01N33/15G01N33/50
CPCC12N15/8509C12N2800/90A01K67/0333A01K67/0339A01K2217/05A01K2227/706A01K2267/0306A01K2267/0312C07K14/4705C07K14/82C12N15/85A61P25/28
Inventor FOGARTY, PATRICKLIPSICK, JOSEPH
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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