Overview

Mice homozygous for the teetering spontaneous mutation (tn) die between 5 and 6 weeks of age. Homozygous mutant mice are first recognizable at 25 to 30 days by their stiff, slow, unstable movements and their growth retardation. They may assume and maintain unusual postures. Occasionally they have running "fits". Just prior to death they look emaciated and lie on their sides with all limbs extended. In the brainstem and spinal cord there is dysgenesis of selective regions including the pons, trapezoid body, olivary and fastigial nuclei, and the pyramidal tract. There is also progressive Purkinje cell loss. Positional cloning reveals that the teetering, tn, mutation is a single nucleotide substitution (adenine to guanine transition at position 265, M89V)in the
Hgs, HGF-regulated tyrosine kinase substrate, gene.

Genetic overview

Genetic Background	Generation

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Hgs^tn

Allele Type	Gene Symbol	Gene Name
Spontaneous (Hypomorph)	Hgs	HGF-regulated tyrosine kinase substrate

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Research Applications

Developmental Biology Research
Neurobiology Research

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Base Price

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$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the teetering spontaneous mutation (tn) die between 5 and 6 weeks of age. Homozygous mutant mice are first recognizable at 25 to 30 days by their stiff, slow, unstable movements and their growth retardation. They may assume and maintain unusual postures. Occasionally they have running "fits". Just prior to death they look emaciated and lie on their sides with all limbs extended. In the brainstem and spinal cord there is dysgenesis of selective regions including the pons, trapezoid body, olivary and fastigial nuclei, and the pyramidal tract. There is also progressive Purkinje cell loss. Positional cloning reveals that the teetering, tn, mutation is a single nucleotide substitution (adenine to guanine transition at position 265, M89V)in the
Hgs, HGF-regulated tyrosine kinase substrate, gene.

Development

The teetering mutation spontaneously arose in the C3H/HeJ inbred strain in 1959 at The Jackson Laboratory. The mutation was backcrossed to C57BL/6J six times and maintained as a sibling mating. In 1979, a high incidence of hydrocephalus in the colony prompted an outcross to B6C3FeF1/J a/a. This strain was cryopreserved as embryos in 1986.

Selected References

Watson JA; Bhattacharyya BJ; Vaden JH; Wilson JA; Icyuz M; Howard AD; Phillips E; DeSilva TM; Siegal GP; Bean AJ; King GD; Phillips SE; Miller RJ; Wilson SM. 2015. Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS. PLoS Genet 11(6):e1005290PubMed: 26115514 MGI: J:221937

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Genetics

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.

Hgs^tn

Allele Symbol: Hgs^tn

Allele Name	teetering
Allele Type	Spontaneous (Hypomorph)
Allele Synonym(s)
Gene Symbol and Name	Hgs, HGF-regulated tyrosine kinase substrate
Gene Synonym(s)
Strain of Origin	C3H/HeJ
Chromosome	11
Molecular Note	A spontaneous A-to-G point mutation results in the amino acid substitution of methionine with valine at position 89 (p.M89V).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Hgs^tn related

Developmental Biology Research
- Neurodevelopmental Defects
Neurobiology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Hgs^tn/Hgs^tn
C3H/HeJ-Hgs

behavior/neurological phenotype

abnormal posture
- just prior to death, homozygotes cannot stand or walk and lie on their sides with all limbs extended

abnormal stationary movement
- homozygotes are first recognizable at 25-30 days of age when their movements become stiff, slow, and unstable

bradykinesia
- homozygotes display slow movements at 25-30 days of age

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - homozygotes display normal hearing

mortality/aging

premature death
- homozygotes become emaciated and die around 5 weeks of age

Genotype: Hgs^tn/Hgs^tn
B6.C3-Hgs

behavior/neurological phenotype

abnormal motor coordination/balance
- at >30 days of age, homozygotes are unstable and walk stiffly

abnormal resting posture
- homozygotes maintain an upright sitting position with their tail and hindlimbs, flexing their forelimbs close to the chest

impaired balance

impaired swimming
- most homozygotes sink rapidly in water

increased stereotypic behavior
- homozygotes repeatedly run in "fits", attepmt to climb the walls and fall over, with feet continuing to pedal vigorously

jerky movement
- homozygotes tend to lurch and launch forward

opisthotonus

paralysis
- homozygotes eventually become paralyzed, are unable to stand and lay on their side with all limbs extended

mortality/aging

premature death
- homozygotes die between 5 and 6 weeks of age

muscle phenotype

muscular atrophy
- centrally located nuclei and nuclear rowing are observed
- fibers are closely packed within bundles
- homozygotes display a uniform muscle atrophy, affecting all fibers; muscles of the lower half of the body appear wasted

opisthotonus

nervous system phenotype

abnormal axon morphology
- in both spinal cord and medulla, afferent axons are swollen but less often than in efferent tracts
- in the medulla, axonal swellings appear as segmental or single coarse thickenings or bulbous-globular enlargements and occur primarily in efferent axons and most frequently in fibers of the tectospinal tract

abnormal brain development
- homozygotes display underdevelopment of certain brain regions
- Normal - however, no heterotopia is observed

abnormal cerebellar cortex morphology
- the mutant cerebellar cortex and most fiber tracts are reduced

abnormal CNS glial cell morphology
- some neuroglia are significantly reduced in number and size while others remain normal

abnormal medulla oblongata morphology
- medullary neurons are smaller than those of control littermates
- the mutant medulla oblongata is smaller than that of controls and small relative to the size of the fore- and mibrain
- the volume of both white and grey matter is reduced

abnormal myelin sheath morphology
- Normal - however, no degeneration, total loss, or accumulation of myelin is observed
- mutant myelin sheaths are smaller and thinner than those of control littermates, resulting in white matter reduction

abnormal spinal cord grey matter morphology
- neurons, glia and glial fibers of the grey matter, and spinal ganglia are smaller than normal
- the funicular and short fiber tracts are smaller than normal
- the mutant spinal cord is deficient in grey matter, with progressive severity caudally

abnormal spinal cord white matter morphology
- the mutant spinal cord is deficient in white matter, with progressive severity caudally

abnormal spinal nerve morphology
- mutant spinal nerves appear smaller than normal

axonal dystrophy
- a few axonal swellings and abnormalities are seen in the medial lemniscus and corticospinal tract caudad to brain stem as well as the dorsal spinocerebellar tract
- a mild axonal dystrophy is observed in the cerebellum, probably involving both the Purkinje cells and granule cell axons

decreased corticospinal tract size
- the mutant pyramidal tract contains less fibers and is markedly smaller than that of control littermates and very small in proprtion to the medulla

decreased hindbrain size
- several structures of the mutant hindbrain are significantly reduced in size

decreased midbrain size
- Normal - in contrast, the overall size of the forebrain and its substructures is normal
- the mutant midbrain is smaller than that of control littermates

decreased neuron number
- homozygotes show a disproportionate decrease in the size and number of neurons in the olivary and fastigial nuclei, spinal cord, and spinal ganglia

decreased pons size
- the pons, trapezoid body, olivary and fastigial nuclei are significantly reduced in size

decreased spinal cord size
- the mutant spinal cord is smaller and shorter than that of control littermates

Purkinje cell degeneration
- basket remnants persist around some cells but are eventually lost
- Purkinje cells of the cerebellum are variably reduced in number
- shrunken Purkinje cells are observed

small cerebellum
- Normal - however, lobular formation and folia are normal
- the mutant cerebellum is slightly smaller than that of control littermates
- the volume of both white and grey matter is reduced

thin cerebellar granule layer
- the mutant cerebellar granule cell layer is smaller than that of control littermates

skeleton phenotype

abnormal vertebral column morphology
- the diameter of the vertebral column is smaller than normal, esp. at the lumbar level of the spinal cord

abnormal vertebral spinous process morphology
- mutant spinous processes are shorter than normal

decreased trabecular bone thickness
- mutant trabeculae and bony spicules are thinner and more delicate than normal

short vertebral body

growth/size/body region phenotype

cachexia
- homozygotes exhibit significant wasting a few days prior to death

decreased body height

decreased body size
- all visceral organs appear normal but are uniformly smaller than normal
- at 30 days of age or later, homozygotes are about 50%-75% the size of control littermates

postnatal growth retardation
- growth retardation is evident by 30 days of age

References

Watson JA; Bhattacharyya BJ; Vaden JH; Wilson JA; Icyuz M; Howard AD; Phillips E; DeSilva TM; Siegal GP; Bean AJ; King GD; Phillips SE; Miller RJ; Wilson SM. 2015. Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS. PLoS Genet 11(6):e1005290PubMed: 26115514 MGI: J:221937

Additional References

Meier H. 1967. The neuropathy of teetering, a neurological mutation in the mouse. Arch Neurol 16(1):59-66PubMed: 6024256 MGI: J:5025

Additional - a related

Additional - Hgs^tn related

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Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the B6C3Fe a/a-Hgs^tn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000245 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
	Homozygous for a, Heterozygous or Homozygous or Wild-type for Hgs<tn>, 1 pair minimum

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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.

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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

a

Allele Symbol: a

Hgstn

Allele Symbol: Hgstn

Disease Terms

Research Areas By Phenotype

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

Genotype: Hgstn related

Mammalian Phenotype Terms by Genotype

Genotype: Hgstn/HgstnC3H/HeJ-Hgs

behavior/neurological phenotype

mammalian phenotype

mortality/aging

Genotype: Hgstn/HgstnB6.C3-Hgs

behavior/neurological phenotype

mortality/aging

muscle phenotype

nervous system phenotype

skeleton phenotype

growth/size/body region phenotype

References

Additional References

Additional - a related

Additional - Hgstn related

Genotyping Protocols

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

Hgs^tn

Allele Symbol: Hgs^tn

Genotype: Hgs^tn related

Genotype: Hgs^tn/Hgs^tn
C3H/HeJ-Hgs

Genotype: Hgs^tn/Hgs^tn
B6.C3-Hgs

Additional - Hgs^tn related