Related Experiment Video
Updated: Apr 8, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Modeling Suggests TRPC3 Hydrogen Bonding and Not Phosphorylation Contributes to the Ataxia Phenotype of the
Sonya M Hanson1,2, Mark S P Sansom2, Esther B E Becker3
1†Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, United States.
Abstract:
A gain-of-function mutation (T635A) in the transient receptor potential (TRP) channel TRPC3 results in abnormal channel gating and causes cerebellar ataxia in the dominant Moonwalker (Mwk) mouse mutant. However, the underlying molecular and structural mechanisms are unclear. Here, we used a combined approach of computational modeling and functional characterization of proposed TRPC3 mutants. Our findings support a mechanism by which the hydrogen bonding capability of threonine 635 plays a significant role in maintaining a stable, closed state channel. This capability is lost in the Mwk mutant, suggesting a structural basis for the disease-causing phenotype in the Mwk mouse.
More Related Videos
07:33A Simple Composite Phenotype Scoring System for Evaluating Mouse Models of Cerebellar Ataxia
Published on: May 21, 2010
10:02Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology
Published on: May 28, 2017