Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice.
Document Type
Article
Publication Date
2006
Keywords
Anterior-Horn-Cells, Carrier-Proteins, Chromosomes-Mammalian, Diazepam, Electromyography, Gene-Expression, Homeostasis, Homozygote, Humans, Inclusion-Bodies, Mice, Molecular-Sequence-Data, Muscle-Hypertonia, Muscle-Skeletal, Mutation, Physical-Chromosome-Mapping, Pons, RNA-Messenger, Receptors-GABA-A
First Page
245
Last Page
250
JAX Source
Nat Genet 2006 Feb; 38(2):245-50.
Abstract
Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.
Recommended Citation
Gilbert SL,
Zhang L,
Forster ML,
Anderson JR,
Iwase T,
Soliven B,
Donahue LR,
Sweet HO,
Bronson RT,
Davisson MT,
Wollmann RL,
Lahn BT.
Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice. Nat Genet 2006 Feb; 38(2):245-50.