Transgenic mouse as model for diseases involving dopaminergic dysfunction

Abstract

The present invention provides a transgenic mouse which exhibits a circling phenotype as a result of insertional mutagenesis. The insertional mutant was caused by introducing genetic material into the genome of the mouse, or an ancestor thereof, at an embryonic stage. The genetic material appears to alter or disrupt an endogenous genetic locus affecting motor function, resulting in the mutation. More particularly, transgenic mouse lines were made by microinjection of about 24 kb XhoI genomic DNA fragment containing the mouse Ren-2.sup.d renin gene into BCF.sub.1, fertilized eggs. One transgenic mouse line, designated TgX15 (also known as chakragati mice), bred to homozygosity was found to exhibit a circling phenotype. The transgenic mouse line TgX15 may be an important resource for investigating the molecular genetic mechanisms that determine specific aspects of brain function and behavior. Also, these mice may be useful to evaluate new and potentially more effective agents for the therapeutic treatment of disorders involving dopaminergic dysfunction such as Parkinsonism and schizophrenia.