Hypertonia results from motor pathway defects in the central nervous system (CNS) and is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson's disease. γ-aminobutyric acid type A (GABA) is a primary inhibitory neurotransmitter of the CNS, and its action is mediated through GABA_A receptors. These receptors are found throughout the CNS, and their proper regulation is essential for setting the inhibitory tone of the CNS and modulating synaptic plasticity.

The spontaneous autosomal recessive mutation hypertonic (hyrt) is a 20 bp deletion in the last exon of the trafficking protein kinesin binding 1 gene (Trak1) on chromosome 9; causing a frameshift after the codon for amino acid 824. Transcription from the mutant locus is not significantly altered, and the resulting C-terminal truncated Trak1 protein's interaction with GABA type A (GABA_A) receptors are not significantly altered.

Homozygous mice (Trak1^hyrt/hyrt) exhibit severe motor defects consistent with hypertonia, including stiff gait, hunched posture, jerky movements and slight tremor. These phenotypes become noticeable around two weeks of age and persist thereafter. Stiffness and jerkiness can be readily felt when manually testing the passive resistance of hindlimbs. While a small percentage of homozygotes die in adolescence, many live out a relatively normal lifespan. Additionally, homozygous mice have reduced levels of GABA_A receptors in their CNS, particularly the lower motor neurons (suggesting the hypertonicity is likely caused by deficits in GABA-mediated motor neuron inhibition). Heterozygous animals are viable and fertile with outwardly normal appearance.These hyrt mice are useful for studying hypertonia, as well as the interaction of Trak1 with GABA_A receptors, and the regulation of GABA_A receptor homeostasis in human neurological disease.