Overview

Also Known As:quaking viable, quaking

These mice carry a spontaneous mutation at the Qk locus characterized by a rapid tremor that increases during locomotion.

Genetic overview

Genetic Background	Generation

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Allele Type	Gene Symbol	Gene Name
Spontaneous	Qk	quaking

Research Applications

Neurobiology Research
Apoptosis Research
Cell Biology Research
Sensorineural Research
Reproductive Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the quaking spontaneous mutation (Qk) have marked rapid tremor which disappears when they are at rest but increases during locomotion. The tremor in homozygous mutant mice begins at about 10 days and is fully developed by 3 weeks. Mature mice may have seizures in which a motionless posture is maintained for many seconds. Females are viable and fertile, males are sterile due to defective spermatic differentiation. The entire CNS of quaking mutant mice is severely deficient in myelin and there is a less severe myelin deficiency in the PNS.

Development

The quaking (Qk^qk) mutation arose spontaneously in 1961 in the DBA/2J strain. It was crossed twice to C3H then transferred to the C57BL/6JEi background via backcross-intercross mating until N10 then sibling bred. At N11F10 it was bred to C57BL/6J-T^2J, and a repulsion stock was generated. In 1976 a Qk^qk homozygote was outcrossed to a B6C3HF1 male, removing the T^2J mutation, and the Qk^qk mutation was maintained via cross-intercross using Qk^qk homozygous females and B6C3F1 males for the cross since homozygous males are sterile. At N8F4 a change was made to use B6C3Fe-a/a F1 for the outcross. In 1987 homozygous females at N15F1 were bred with B6C3F3-a/a F1 males to generate embryos for cryopreservation.

Control Suggestions

Untyped from the colony

Additional Information

Considerations for Choosing Controls

Selected References

SIDMAN RL; DICKIE MM; APPEL SH. 1964. MUTANT MICE (QUAKING AND JIMPY) WITH DEFICIENT MYELINATION IN THE CENTRAL NERVOUS SYSTEM. Science 144:309-11PubMed: 14169723 MGI: J:13141

View All References

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.

Qk^qk-v

Allele Symbol: Qk^qk-v

Allele Name	quaking viable
Allele Type	Spontaneous
Allele Synonym(s)	qk; Qk^qk; qk^v
Gene Symbol and Name	Qk, quaking
Gene Synonym(s)
Strain of Origin	DBA/2J
Chromosome	17
General Note	The quaking mutation arose spontaneously in the DBA/2J strain. Homozygotes have marked rapid tremor which disappears when they are at rest but increases during locomotion. It begins at about 10 days and is fully developed by 3 weeks. Mature mice may have seizures in which a motionless posture is maintained for many seconds. Females are viable and fertile, males sterile.Homozygotes are severely deficient in myelin, the material which ensheathes and insulates the axons of the central (CNS) and peripheral (PNS) nervous systems (see Mbp). The entire CNS is very deficient in myelin at all ages (J:13141), and there is a less severe myelin deficiency in the PNS nervous system (J:5177). Myelin sheaths are present in the CNS, but they are thinner than normal, some consisting of only one to four myelin lamellae. The sheaths are usually loosely wound, with patches of oligodendroglial cell cytoplasm between the lamellae, and there are abnormal inclusions and vacuoles in the processes and perikarya of oligodendrocytes. Development of the myelin sheaths appears to be arrested in a stage characteristic of very young animals (J:5189)(J:5271)(J:5218). There is variable hyperplasia of oligodendrocytes, greatest in the tracts with the greatest degree of myelination (J:5615). Axons have normal morphology but there is abnormally high proteolysis in the axons of the optic nerve (J:6971). There is evidence that the myelination defect in the CNS is due to defective oligodendrocytes (J:6216).Handling-induced convulsive seizures in qk/qk mice can be inhibited by administration of N-methyl-D-aspartate (NMDA) antagonists. Modulatory mechanisms for the NMDA receptor complex may differ in qk/qk mice from wild-type (J:1930). a2-adrenoceptor (A2A) antagonists also inhibit these seizures, while A2A agonists potentiate them. qk/qk mice have increased brain binding sites for A2A agonists (J:1169).In the PNS, thinly myelinated and unmyelinated fibers have been described in the sciatic nerve and in the intracranial portion of the trigeminal nerve (J:5189)(J:5271). The sheaths may be structurally abnormal with regions of uncompacted myelin lamellae similar to those of the CNS (J:5778). Orthotopic transplantation of pieces of sciatic nerve between quaking and normal mice has shown that the genetic defect is expressed in Schwann cells (J:14892). Qk causes defective myelinogenesis in both oligodendrocytes and Schwann cells (J:6411).There is an extensive literature on biochemical defects related to the deficiency of myelin in quaking mice (J:26986), a consistent finding of which is a severe deficiency of the myelin lipids, sphingomyelin, cerebrosides, and sulfatides, particularly those containing long-chain fatty acids. The normal increase in these fatty acids which occurs between 15 and 20 days does not occur in qk/qk mice, so that adult mutants tend to resemble very young controls (J:5171). Brain proteolipids in adult quaking mice retain the relative proportions found in 10-day controls (J:5408). The myelin-associated glycoproteins of different molecular weight in the brains of quaking mice 15 days of age and older are expressed in abnormal proportions (J:7990). Synthesis of myelin basic protein and proteolipids is normal in quaking brains but their incorporation into myelin is defective (J:6151). mRNAs for myelin basic protein, for example, occur in oligodendrocyte cell bodies, but not in the cell processes that actually form the myelin sheath, in qk/qk brain (J:1931). Quaking mice may have abnormal levels of copper and zinc in the brain, but the evidence on this point is conflicting (J:7214).The sterility of male qk/qk mice is due to defective spermatid differentiation, the details of which have been described (J:5241). It has been further demonstrated that male sterility in these mice is the result of the loss of Pacrg expression (J:90667).
Molecular Note	The quaking phenotype has been attributed to a 1.85 Mb deletion on chromosome 17. The proximal breakpoint was located in the promoter region of the Qk gene and affects transcript levels of that gene. The distal breakpoint lies between exons 5 and 6 of the parkin gene. Both the parkin gene and another co-regulated gene, Pacrg, are inactivated. Although parkin is not expressed in these mutants, the described phenotype appears due to to the defect in Qk expression.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Parkinson's Disease
  - Park2 (parkin) mutants

Genotype: Qk^qk-v related

Apoptosis Research
Neurobiology Research
- Epilepsy
- Myelination Defects
- Parkinson's Disease
- Neurodegeneration
- Tremor Defects
- Hearing Defects
Cell Biology Research
- Cell Cycle Regulation
- Protein Processing
  - degradation
Sensorineural Research
- Hearing Defects
Reproductive Biology Research
- Developmental Defects Affecting Gonads
  - males only
- Fertility Defects
  - males only

Mammalian Phenotype Terms by Genotype

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

Genotype: Qk^qk-v/Qk^qk-v
involves: DBA/2J

behavior/neurological phenotype

abnormal gait
- walk slowly with a trembling gait

abnormal locomotor behavior
- decrease in the frequency of wire mesh climbing in males

abnormal response to novel object
- decrease in the frequency of exploratory sniffing (at wire mesh or a novel object) and leans against the novel object in males

abnormal stationary movement
- decrease in the frequency of leaning against the wall or a novel object and single forepaw lifts in males

hypoactivity

increased grooming behavior
- increase in the frequency of hair fluffing in males

Genotype: Qk^qk-v/Qk^qk-v
involves: C3H/Di * DBA/2J

behavior/neurological phenotype

paraparesis
- some animals exhibit hindlimb weakness at 3 months of age

tonic seizures
- following swimming, some mice become motionless and then display a tonic extension of hindlimbs for several minutes
- some mice exhibit adduction of limbs under a flexed trunk and then become stiff and motionless for several seconds

tremors
- in some animals, tremors diminish at 3 months
- physical contact with the mouse reduces or stops tremors
- tremors are first observed at 10-12 days of age and reach full expression by 3 weeks
- tremors are most evident in the caudal part of the trunk and proximal portions of hind extremities
- visually, the rate of tremors are 2 to 3 per second

reproductive system phenotype

reduced male fertility
- male homozygotes rarely sire offspring

nervous system phenotype

abnormal myelination
- cells in white matter and grey matter tracts appear normal
- cranial and spinal nerves (except optic nerve) are myelinated
- loss of myelination begins at the junction of peripheral and central nervous systems
- region from olfactory bulb to sacral spinal cord is deficient in myelin at all ages studied (12 days to 4 months)
- some fragments of myelin are seen in almost all fiber tracts

tonic seizures
- following swimming, some mice become motionless and then display a tonic extension of hindlimbs for several minutes
- some mice exhibit adduction of limbs under a flexed trunk and then become stiff and motionless for several seconds

The following phenotype relates to a compound genotype created using this strain

Genotype: Qk^qk-v/Qk^qk-v
B6C3Fe a/a-Qk/J

behavior/neurological phenotype

seizures
- onset of seizures begins at 6-8 weeks of age; seizures occur less frequently than in homozygous Qk^e5 mice

reproductive system phenotype

abnormal sperm flagellum morphology

abnormal sperm head morphology

abnormal spermatogenesis
- acytoplasmic sperm injection and round spermatid injection are successful in production of offspring from homozygous males
- the testis contain many spermatogenic cells, but few spermatozoa and the spermatozoa collected from the cauda epididymis all have abnormal heads and/or tails and less than 0.5% are barely motile, and although in vitro fertilization is not successful, intracytoplasmic sperm injection and round spermatid injection are successful in production of offspring from homozygous males

abnormal spermiogenesis

necrospermia

oligozoospermia

cellular phenotype

abnormal sperm flagellum morphology

abnormal sperm head morphology

necrospermia

oligozoospermia

hearing/vestibular/ear phenotype

reduced linear vestibular evoked potential
- prolonged latency for all peaks and larger amplitudes for P1/N1

nervous system phenotype

abnormal myelination
- decrease in myelination, however more axons are surrounded by thin myelin sheaths than seen in Qk^e5 homozygotes
- microsomes prepared from brains of 18 day old homozygotes show a reduction in fatty acid chain elongation activity with arachidoyl CoA, behenoyl CoA, and palmitoyl CoA substrates

Purkinje cell degeneration
- aging mutants exhibit Purkinje cell axonal swellings, indicating neurodegeneration

seizures
- onset of seizures begins at 6-8 weeks of age; seizures occur less frequently than in homozygous Qk^e5 mice

References

SIDMAN RL; DICKIE MM; APPEL SH. 1964. MUTANT MICE (QUAKING AND JIMPY) WITH DEFICIENT MYELINATION IN THE CENTRAL NERVOUS SYSTEM. Science 144:309-11PubMed: 14169723 MGI: J:13141

Additional References

Mitrovic N; Caboche J; Carre JB; Besson MJ; Maurin Y. 1991. The quaking mouse: an epileptic mutant with alterations affecting the modulatory mechanisms of the NMDA receptor complex. Brain Res 566(1-2):248-54PubMed: 1839963 MGI: J:1930
Yanagimachi R; Wakayama T; Kishikawa H; Fimia GM; Monaco L; Sassone-Corsi P. 2004. Production of fertile offspring from genetically infertile male mice. Proc Natl Acad Sci U S A 101(6):1691-5PubMed: 14757819 MGI: J:88151

Additional - a related

Additional - Qk^qk-v related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Qk
- Genotyping resources and troubleshooting
Breeding Considerations

Comments: homozygous males are sterile.
- Additional Breeding and Husbandry Support
Appearance
- black, tremors
  Related Genotype: a/a Qk^qk/Qk^qk
  
  black, unaffected
  Related Genotype: a/a Qk^qk/+ or a/a ?/+
Citation
When using the quaking viable mouse strain in a publication, please cite the originating article(s) and include JAX stock #000506 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 for Qk<qk>

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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General Terms and Conditions

Questions about Terms of Use

Licensing Information

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Also Known As:quaking viable, quaking

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

a

Allele Symbol: a

Qkqk-v

Allele Symbol: Qkqk-v

Disease Terms

Research Areas By Phenotype

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

Genotype: Qkqk-v related

Mammalian Phenotype Terms by Genotype

Genotype: Qkqk-v/Qkqk-vinvolves: DBA/2J

behavior/neurological phenotype

Genotype: Qkqk-v/Qkqk-vinvolves: C3H/Di * DBA/2J

behavior/neurological phenotype

reproductive system phenotype

nervous system phenotype

Genotype: Qkqk-v/Qkqk-vB6C3Fe a/a-Qk/J

behavior/neurological phenotype

reproductive system phenotype

cellular phenotype

hearing/vestibular/ear phenotype

nervous system phenotype

References

Additional References

Additional - a related

Additional - Qkqk-v related

Genotyping Protocols

Breeding Considerations

Appearance

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

Qk^qk-v

Allele Symbol: Qk^qk-v

Genotype: Qk^qk-v related

Genotype: Qk^qk-v/Qk^qk-v
involves: DBA/2J

Genotype: Qk^qk-v/Qk^qk-v
involves: C3H/Di * DBA/2J

Genotype: Qk^qk-v/Qk^qk-v
B6C3Fe a/a-Qk/J

Additional - Qk^qk-v related