TITLE
Ankyrin-G Conditional Forebrain Knockout Mouse Model of Human Psychiatric Disorders
CASE NUMBER
C13170
ABSTRACT
The Ankyrin-G locus has emerged from Genome-Wide Association Studies as one of the risk factors for human psychiatric disorders. It has been positive mainly in studies of bipolar disorder, but also in some studies of schizophrenia. Ankyrin-G is well known for its role in organizing the axon initial segment, by binding proteins such as voltage-gated sodium and potassium channels, and thus establishing the machinery for the generation of the action potential. There are some data consistent with the idea that the alteration in the human psychiatric disorders might be a genetic loss of function. Johns Hopkins researchers have generated a conditional knockout of Ankyrin-G in the forebrain, using a mouse line with a floxed allele for Ankyrin-G.
FEATURES
Johns Hopkins researchers generated an Ankyrin-G conditional forebrain knockout mouse mode by crossing a mouse line with floxed allele and one expressing Cre. This Floxed allele Ankyrin-G knockout mouse model knock out all major functional isoforms of Ankyrin-G in the brain compared to previous model that only deletes one particular isoform. The Ankyrin-G forebrain homozygous conditional knockouts have:
striking behavioral hyperactivity and changes in emotional behavior, without substantial abnormalities of sensory-motor gating.
Mechanisms include loss of presynaptic GABA inhibitory terminals on the axon initial segment.
changes in the ratio of sodium and potassium channels in the axon initial segment.
Psychiatric disorders drugs such as Lithium, Valproate and Clozapine ameliorate the behavioral phenotype.
Can be used to study the mechanism of known therapeutics.
Use as a platform to test novel experimental therapeutics to treat human psychiatric illnesses.
STAGE OF DEVELOPMENT
Tangible material, Ankyrin-G Conditional Forebrain Knockout mouse model.
DISEASE INDICATION
Psychiatric Disorders
ASSOCIATED PUBLICATIONS
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):10479-10484
TECHNOLOGY CLASSIFICATION
Primary Category: Discovery/Research Tools
Primary Subcategory: In Vivo Research Tool
