The spontaneous autosomal recessive mutation hypertonic (hyrt) is a 20 bp deletion in the last exon of the Trak1 gene on chromosome 9 which results in a C-terminal truncated mutant protein. These hyrt mice may be useful for studies related to hypertonia, as well as the detailed aspects of Trak1 and GABAA receptor interactions.Read More +
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 GABAA 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 (GABAA) receptors are not significantly altered.
Homozygous mice (Trak1hyrt/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 GABAA 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 GABAA receptors, and the regulation of GABAA receptor homeostasis in human neurological disease.
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. The history of Stock No. 003612 is described below.
The hyrt mutation arose spontaneously at The Jackson Laboratory in the inbred strain AKR/J in early 1993 when that strain was at generation F197. This mutation was maintained four generations four generations on the AKR/J background, and then outcrossed to a B6C3Fe a/a F1 hybrid (Stock No. 001022). It was maintained thereafter by outcross-intercross using B6C3Fe a/a males bred either with homozygous females or hosts of ovaries transplanted from homozygotes. In 1999-2000, heterozygous embryos were cryopreserved at generation N7 (i.e., seven generations of outcrossing to the B6C3Fe a/a F1). By 2006, the live colony reached generation N17F1 when it was removed from live shelf in 2006. In 2014, heterozygous frozen embryos (generation N7) were reanimated to establish the living colony.
|Allele Synonym(s)||Trak1hyrt; hypertonic|
|Gene Symbol and Name||Trak1, trafficking protein, kinesin binding 1|
|Gene Synonym(s)||2310001H13Rik; expressed sequence AI467545; hypertonic; RGD1307844; 2310001H13Rik; RIKEN cDNA 2310001H13 gene; MILT1; AI467545; hyrt; AI413908; hyrt; nm1952; OIP106; expressed sequence AI413908; EIEE68|
|Strain of Origin||AKR|
|Molecular Note||There is a 20 bp deletion in the last exon of the gene. This results in a frame shift after the codon for amino acid 824. 12% of the protein is disrupted.|
|Allele Synonym(s)||nonagouti; a|
|Gene Symbol and Name||a, nonagouti|
|Gene Synonym(s)||agouti signal protein; As; ASP; As; agouti; agouti suppressor; AGTI; SHEP9; AGSW; AGTIL|
|Strain of Origin||old mutant of the mouse fancy|
|General Note||Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039|
|Molecular Note||Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for at-2Gso and Aw-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.|
The live colony at The Jackson Laboratory is maintained by alternating generations of outcross-intercross. That is:
i. Heterozygous mice (Trak1hyrt/+) are bred together. The resulting homozygous animals are used for step ii below.
ii. Homozygous females (Trak1hyrt/hyrt) are bred to B6C3FeF1/J a/a males (Stock No. 001022). The resulting heterozygous mice are used for step i above.
When using the B6C3Fe a/a-Trak1hyrt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003612 in your Materials and Methods section.
|Heterozygous or Wild-type for Trak1<hyrt>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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