Overview

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 GABA_A receptor interactions.

Genetic overview

Genetic Background	Generation

Trak1^hyrt

Allele Type	Gene Symbol	Gene Name
Spontaneous	Trak1	trafficking protein, kinesin binding 1

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

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Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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.

Control Suggestions

+/? from the colony

Additional Information

Considerations for Choosing Controls

Genetics

Trak1^hyrt

Allele Symbol: Trak1^hyrt

Allele Name	hypertonic
Allele Type	Spontaneous
Allele Synonym(s)	hyrt; nm1952
Gene Symbol and Name	Trak1, trafficking protein, kinesin binding 1
Gene Synonym(s)
Strain of Origin	AKR
Chromosome	9
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.

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
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 a^t-2Gso and A^w-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.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Stiff-Person syndrome

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Developmental Biology Research
- Postnatal Lethality
  - Homozygous
- Neurodevelopmental Defects
Neurobiology Research
- Ataxia (Movement) Defects
- Receptor Defects
  - GABA receptor
- Neuromuscular defects
- Tremor Defects
- Channel and Transporter Defects
  - chloride: GABAA receptor
Research Tools
- Neurobiology Research
Cell Biology Research
- Channel and Transporter Defects
  - chloride: GABAA receptor

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Trak1^hyrt/Trak1^hyrt
B6C3Fe a/a-Trak1/J

behavior/neurological phenotype

abnormal posture

impaired coordination

weakness
- display hypertonicity and spasticity
- weakness

Genotype: Trak1^hyrt/Trak1^hyrt
involves: AKR * C3HeB/FeJ * C57BL/6J

behavior/neurological phenotype

abnormal gait
- first noticeable at 2 weeks of age
- stiff gait

hunched posture
- first noticeable at 2 weeks of age

jerky movement
- first noticeable at 2 weeks of age

tremors
- first noticeable at 2 weeks of age
- slight tremors

nervous system phenotype

abnormal neuron morphology
- become detectable at 2-4 weeks of age
- inclusions found in neuronal processes only, possibly in dendrites
- oval shaped aggregates of vescicular structures with 2-layer membranes in the gray matter of brainstem and spinal cord

mortality/aging

premature death
- some deaths among adolescent mice but most have normal life spans

muscle phenotype

abnormal muscle physiology
- highly elevate baseline motor unit activity in muscles of both forelimb and hind limb
- motor unit activity reduced by diazepam which enhances GABAergic transmission

References

Additional - a related

Additional - Trak1^hyrt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Trak1
- Sanger sequencing:Trak1-SEQ
- Genotyping resources and troubleshooting
Breeding Considerations

The live colony at The Jackson Laboratory is maintained by alternating generations of outcross-intercross. That is:
i. Heterozygous mice (Trak1^hyrt/+) are bred together. The resulting homozygous animals are used for step ii below.
ii. Homozygous females (Trak1^hyrt/hyrt) are bred to B6C3FeF1/J a/a males (Stock No. 001022). The resulting heterozygous mice are used for step i above.
- Additional Breeding and Husbandry Support
Mating System
- homozygous not transplanted or ovarian transplant x B6C3Fe-a/a F1 then obligate heterozygote x heterozygot
Citation
When using the B6C3Fe a/a-Trak1^hyrt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003612 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Trak1<hyrt>

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Trak1hyrt

Allele Symbol: Trak1hyrt

a

Allele Symbol: a

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Trak1hyrt/Trak1hyrtB6C3Fe a/a-Trak1/J

behavior/neurological phenotype

Genotype: Trak1hyrt/Trak1hyrtinvolves: AKR * C3HeB/FeJ * C57BL/6J

behavior/neurological phenotype

nervous system phenotype

mortality/aging

muscle phenotype

References

Additional - a related

Additional - Trak1hyrt related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Trak1^hyrt

Allele Symbol: Trak1^hyrt

Genotype: Trak1^hyrt/Trak1^hyrt
B6C3Fe a/a-Trak1/J

Genotype: Trak1^hyrt/Trak1^hyrt
involves: AKR * C3HeB/FeJ * C57BL/6J

Additional - Trak1^hyrt related