Overview

Also Known As:rocker

Rocker (rkr) mutant mice possess an ENU-induced point mutation in the Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) gene. Homozygous mice exhibit mild ataxia, absence seizures, and abnormal dendritic branching in Purkinje cells. They may be useful for studies of voltage-dependent calcium channels and as an additional phenotype for the Cacna1a allelic series.

Donating Investigator

Hyder Jinnah, Emory University

Genetic overview

Genetic Background	Generation

Cacna1a^rkr

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Cacna1a	calcium channel, voltage-dependent, P/Q type, alpha 1A subunit

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Research Applications

Neurobiology Research
Cell Biology Research

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Details

Detailed Description

Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) is expressed in neuronal tissue and encodes the pore-forming alpha1a subunit, which directs activity of the CaV2.1 voltage-gated calcium channel. Mutations in CACNA1A are associated with ataxia and migraines. Mice homozygous for the rocker (rkr) ENU-induced allele exhibit splayed hindlimbs, a mildly ataxic gait, absence seizures, abnormal ocular motor behavior and impaired synaptic transmission in parallel fiber Purkinje cells (PF-PC). Dendrites from Purkinje cells have less arborization, reduced length, and a "weeping willow" appearance. The rocker phenotype is less severe than in other Cacna1a mutants (tottering, leaner). Heterozygotes are viable and fertile. These mutant mice may be useful for studies of voltage-dependent calcium channels and as an additional phenotype for the Cacna1a allelic series.

Development

Male mice from a mixed background were treated with multidose N-ethyl-N-nitrosourea (ENU); in the fourth generation of breeding, ataxic mice were observed. To analyze the mutation these mice were crossed to C57BL/6 mice for five generations. The rocker (rkr) mutation is a C to A transversion at position 3929 of the Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) gene. The mutation alters the corresponding amino acid from threonine to lysine at amino acid 1310 (T1310K) in an extracellular loop located between transmembrane regions 5 and 6 of the third homologous domain. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Zwingman TA; Neumann PE; Noebels JL; Herrup K. 2001. Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci 21(4):1169-78PubMed: 11160387 MGI: J:71860

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Genetics

Cacna1a^rkr

Allele Symbol: Cacna1a^rkr

Allele Name	rocker
Allele Type	Chemically induced (ENU)
Allele Synonym(s)	rkr
Gene Symbol and Name	Cacna1a, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Gene Synonym(s)
Strain of Origin	mixed
Chromosome	8
Molecular Note	A C to A transversion mutation at position 4073 (c.C>A4073) predicts a nonconservative threonine to lysine substitution at position 1358 (p.T1358K) in the extracellular pore-forming loop region that connects segments 5 and 6 of repeat III of the encoded protein.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Epilepsy
- Channel and Transporter Defects
  - calcium
- Ataxia (Movement) Defects
- Cerebellar Defects
  - Purkinje cell defect
Cell Biology Research
- Channel and Transporter Defects
  - calcium

Mammalian Phenotype Terms by Genotype

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

Genotype: Cacna1a^rkr/Cacna1a^rkr
B6.Cg-Cacna1a

behavior/neurological phenotype

abnormal gait
- ataxic gait initiated by an action tremor at 3-4 weeks of age, however do not display paroxysmal dyskinesia
- splayed stance of hindlimbs and clumsy, uncoordinated behavior, especially on uneven surfaces

tremors
- action tremor at 3-4 weeks of age

absence seizures
- spontaneous appearance of bilaterally synchronous and symmetrical 6-7 Hz spike-wave discharges while awake
- episodes occur at a mean frequency range of 41-65 episodes per hour and a mean burst duration of 1-1.7 sec

abnormal locomotor coordination

ataxia
- onset at P21-28

nervous system phenotype

abnormal Purkinje cell dendrite morphology
- shafts of main Purkinje dendrites show a thickening in the upper molecular layer
- abnormal secondary outgrowth of the tips of the distal dendrites
- Purkinje cell arbor is reduced in dendritic mass and complexity in mice over 1 year of age

absence seizures
- spontaneous appearance of bilaterally synchronous and symmetrical 6-7 Hz spike-wave discharges while awake
- episodes occur at a mean frequency range of 41-65 episodes per hour and a mean burst duration of 1-1.7 sec

References

Zwingman TA; Neumann PE; Noebels JL; Herrup K. 2001. Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci 21(4):1169-78PubMed: 11160387 MGI: J:71860

Additional - Cacna1a^rkr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Cacna1a-EP
- Genotyping resources and troubleshooting
Breeding Considerations

The donating investigator maintained this strain as a female heterozygote x male homozygote mating.
- Additional Breeding and Husbandry Support
Citation
When using the rocker mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36812 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

The Jackson Laboratory's Genotype Promise

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:rocker

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Cacna1arkr

Allele Symbol: Cacna1arkr

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cacna1arkr/Cacna1arkrB6.Cg-Cacna1a

behavior/neurological phenotype

nervous system phenotype

References

Additional - Cacna1arkr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Cacna1a^rkr

Allele Symbol: Cacna1a^rkr

Genotype: Cacna1a^rkr/Cacna1a^rkr
B6.Cg-Cacna1a

Additional - Cacna1a^rkr related