Neurological disease model

Abstract

There is provided the use of a metabotropic glutamate receptor mGluR7 agonist for the facilitation of neurotransmitter release from a nerve ending and the treatment of neurological conditions, including epilepsy. Moreover, the invention provides transgenic knockout non-human mammals lacking the mGluR7 gene, suitable for studying mGluR7 and modulators thereof as well as epilepsy.

1 . A transgenic non-human mammal in which the endogenous mGlu 7  gene has been inactivated.  
     
     
         2 . A transgenic non-human mammal according to  claim 1  which has been further manipulated in order to insert a heterologous transgene or delete another endogenous gene.  
     
     
         3 . A transgenic non-human mammal according to  claim 1  or  claim 2  wherein the endogenous mGlu 7  gene is conditionally inactivated.  
     
     
         4 . A method for screening a compound or a mixture of compounds for agonist or antagonist activity in respect of mGlu 7 , comprising exposing a transgenic non-human mammal according to any one of  claims 1  to  3  to the compound or mixture of compounds, and comparing the observed activity thereof to their observed or expected activity in an mGlu 7  expressing mammal.  
     
     
         5 . A method according to  claim 4  wherein the activity of the compound or mixture of compounds is assessed by observing the behavioural effect thereof on the mammals.  
     
     
         6 . A method according to  claim 4  wherein the activity of the compound or compounds is assessed by electrophysiological measurement of neural activity.  
     
     
         7 . A method for screening a compound or a mixture of compounds for agonist or antagonist activity in respect of mGlu 7 , comprising exposing a cell lacking a functional mGlu 7  gene to the compound or mixture of compounds, and comparing the observed activity thereof to their observed or expected activity in an mGlu 7  expressing cell.  
     
     
         8 . Use of a metabotropic glutamate receptor mGlu 7  agonist for the facilitation of neurotransmitter release from a cell by mGlu 7  stimulation.  
     
     
         9 . Use of a metabotropic glutamate receptor mGlu 7  antagonist for the inhibition of neurotransmitter release from a cell by mGlu 7  inhibition.  
     
     
         10 . Use of an mGlu 7  agonist in the manufacture of a composition for the treatment of seizure.