Abstract
More than one billion people worldwide suffer from a neurological disorder. Cholinergic circuits have been implicated in abnormal motor, cognitive and autonomic functioning and are involved in cognitive impairments observed in these disorders. Choline transport via the neuronal high-affinity choline transporter (CHT) is rate-limiting for acetylcholine (ACh) synthesis and release by cholinergic terminals. A coding substitution in the CHT gene (SLC5A7) Ile89Val leads to loss of function of CHT in transfected cells. In humans, the variant is associated with distractibility and increases risk for ADHD, depression and other cholinergic disorders.
Researchers at Florida Atlantic University have used CRISPR/Cas9 techniques to generate a mouse model expressing the human Ile89Val substitution to study and treat cholinergic disorders. Val89 mice exhibit up to an 80% reduction in choline clearance and experience deficits in attentional control when challenged with a visual distractor.
FAU seeks partners to advance this technology into the marketplace through licensing or development partnerships.
Benefit
Disease Research - A humanized mouse model expressing the common, functional human coding variant I89V for the evaluation of cholinergic contributions to brain and peripheral disordersDrug Development - Novel compounds can be evaluated in CHT I89V mice to develop medication leads in human subjects Market Application
Neurological ResearchAutonomic ResearchDrug ScreeningAnimal ModelsPublications
Disrupted Choline Clearance and Sustained Acetylcholine Release In Vivo by a Common Choline Transporter Coding Variant Associated with Poor Attentional Control in Humans
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