Mass 1 gene, a target for anticonvulsant drug development

Abstract

The present invention relates to a novel gene which is associated with audiogenic seizures in mice. The gene is known as the Monogenic Audiogenic Seizure-susceptible gene or mass1. The product of the mass1 gene is designated MASS1. Nucleic acid molecules that encode for MASS1 have been identified and purified. The sequence of murine mass1 can be found at SEQ ID NO: 1, and the sequence of human mass1 can be found at SEQ ID NO: 3. Mammalian genes encoding a MASS1 protein are also provided. The invention also provides recombinant vectors comprising nucleic acid molecules that code for a MASS1 protein. These vectors can be plasmids. In certain embodiments, the vectors are prokaryotic or eukaryotic expression vectors. The nucleic acid coding for MASS1 can be linked to a heterologous promoter. The invention also relates to transgenic animals in which one or both alleles of the endogenous mass1 gene is mutated.

1 . A transgenic mammal wherein one or both alleles of the endogenous mass 1 gene is mutated.  
     
     
         2 . The transgenic mammal of  claim 1 , wherein the mammal is a mouse.  
     
     
         3 . The transgenic mammal of  claim 2 , wherein the mutation results in a seizures susceptible phenotype.  
     
     
         4 . The transgenic mammal of  claim 1 , wherein the mutation results from the insertion of a selectable marker gene sequence or other heterologous sequence into the genome by homologous recombination.  
     
     
         5 . A cell derived from the mammal of  claim 1 .  
     
     
         6 . A cell derived from the mammal of  claim 2 .  
     
     
         7 . A cell derived from a transgenic mammal wherein one or both alleles of the endogenous mass 1 gene is mutated, the mutation resulting from insertion of a selectable marker gene sequence or other heterologous sequence into the genome by homologous recombination, wherein the mutation results in a seizure-susceptible phenotype.  
     
     
         8 . A transgenic mouse whose somatic and germ cells comprise a mutated mass 1 gene, said mutated gene being introduced into the mouse or an ancestor of the mouse at an embryonic stage, the mutation being sufficient to result in a seizure-susceptible phenotype.  
     
     
         9 . A cell derived from the mouse of  claim 8 .  
     
     
         10 . A transgenic mouse whose genome is heterozygous for an engineered mutation in the mass 1 gene, wherein the engineered mutation in a homozygous state results in a seizure-susceptible phenotype.  
     
     
         11 . A cell derived from the mouse of  claim 10.