Abstract: A method, called GETWISE, for targeting mouse genes is described. GETWISE is designed to increase the frequency of homologous recombination, facilitate screening, widen the applicability of engineered animals and circumvent intrinsic gene targeting problems. GETWISE utilizes the principle of modulating gene expression by targeting tetracycline-responsive elements into a specific locus. In GETWISE alleles, control of gene expression is transferred from the endogenous to a tetracycline-inducible promoter. Endogenous promoters now control expression of the reporter gene luciferase. Breeding of GETWISE carriers with tTA/rtTA carriers enables investigators to modulate gene expression in a ubiquitous or tissue-specific manner, depending on the presence of doxycycline. GETWISE enables the study of loss or gain of gene expression in any tissue of choice within a single mouse strain. GETWISE enables the analysis of the gene expression pattern with the luciferase assay.

Abstract: Methods and compositions for modulating GABA release in a subject are provided. A preferred embodiment provides a composition containing an effective amount of an ErbB4 ligand to enhance or promote GABA release, i.e., GABAergic transmission. The ErbB4 ligand can be an agonist ligand or an antagonist ligand depending on the disorder to be treated. Methods for treating neurological disorders are also provided. Representative disorders that can be treated include, but are not limited to schizophrenia, epilepsy, depression and anxiety, insomnia, stroke, pain, bipolar, autism, or a combination thereof. By increasing GABA release a sedative effective can be induced in the subject. Methods for inducing a stimulatory effect in a subject are also provided. In these methods, an effective amount of an ErbB4 antagonist ligand is administered to the subject to reduce or inhibit GABA release in the subject.