Proteins related to schizophrenia and uses thereof

Abstract

Presenilin Associated Membrane Protein (PAMP), and nucleic acids encoding this protein, are provided. PAMP and PAMP nucleic acids provide diagnostic and therapeutic tools for evaluating and treating or preventing neurodevelopmental and neuropsychiatric disorders. In a specific embodiment, mutations in PAMP are diagnostic for schizophrenia. The invention further relates to screening, particularly using high-throughput screens and transgenic animal models, for compounds that modulate the activity of PAMP and presenilins. Such compounds, or gene therapy with PAMP, can be used in treating neurodevelopmental and neuropsychiatric disorders, particularly schizophrenia. In addition, the invention provides PAMP mutants, nucleic acids encoding for PAMP mutants, and transgenic animals expressing PAMP mutants, which in a preferred aspect result in biochemical, morphological, or neuropsychological changes similar to those associated with schizophrenia.

1 . A method for detecting a mutation in presenilin associated membrane protein (PAMP) associated with a neuropsychiatric or neurodevelopmental disorder, which method comprises detecting a variation in a sequence of a gene encoding PAMP obtained from an individual diagnosed with or suspected of having said disorder.  
     
     
         2 . The method of  claim 1 , wherein the disorder is schizophrenia.  
     
     
         3 . A method for diagnosing individuals predisposed to or having a neuropsychiatric or neurodevelopmental disorder, which method comprises detecting a mutation in a gene encoding PAMP obtained from an individual.  
     
     
         4 . The method of  claim 3 , wherein the disorder is schizophrenia.  
     
     
         5 . The method according to  claim 3 , wherein detection of the mutation comprises measuring a level of transcriptional activity of the gene.  
     
     
         6 . he method according to  claim 3 , wherein detection of the mutation comprises measuring PAMP activity.  
     
     
         7 . The method of  claim 6 , wherein said PAMP activity comprises PAMP expression level or activity of a product of a PAMP modified substrate.  
     
     
         8 . A method for identifying a compound that is useful in treating a neuropsychiatric or neurodevelopmental disorder, which method comprises detecting modulation of of PAMP expression in a transgenic animal that expresses PAMP, wherein the animal is contacted with the compound.  
     
     
         9 . The method of  claim 8 , wherein the disorder is schizophrenia.  
     
     
         10 . (canceled)  
     
     
         11 . (canceled)  
     
     
         12 . A method for identifying a compound that is useful in treating a neuropsychiatric or neurodevelopmental disorder, which method comprises: 
 (a) contacting a complex between a presenilin associated membrane protein (PAMP) and an agent, which agent provides a detectable conformational or functional change in said PAMP upon interaction with a substance being analyzed for activity against a neurodegenerative disease, with a test compound; and    (b) detecting a conformational or functional change in PAMP in the complex.    
     
     
         13 . The method of  claim 12 , wherein the disorder is schizophrenia.  
     
     
         14 . The method of  claim 12 , wherein the test compound is a protein that interacts with PAMP.  
     
     
         15 . A method for treating neuropsychiatric or neurodevelopmental disorder in a mammalian host which expresses at least one PAMP protein or a naturally occurring variant, which method comprises administering to the host an amount of compound effective to modulate PAMP expression in the host.  
     
     
         16 . The method of  claim 15 , wherein the disorder is schizophrenia.