Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B10(Cg)-Cacna1aTg-5J/LetJ    (Changed: 25-APR-11 ) Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse H2 Haplotype b

Description
Mice heterozygous for the semi-dominant Tottering 5 Jackson mutation exhibit a shaky gait with hind limbs splayed laterally from the body in contrast to the other tottering mutants . Also, unlike tottering mice, Tg-5J heterozygotes do not exhibit dyskinesia or absence seizures. Axonal swelling is observed in Purkinje cells from homozygotes as well as a decrease in branching. The Tg-5J mutation causes a shift in voltage activation and inactivation to lower voltages. This strain may be useful for studies of epilepsy and voltage-dependent calcium channels.

The C57BL/10J background appears to be embryonic lethal as no homozygotes are produced in heterozygote x heterozygote matings. On a mixed BALB/cByJ and C57BL/10J background some homozygotes are produced, but die before 6 weeks of age.

Development
This spontaneous mutation arose in strain B10.M-H2^f/nMob Fmn1^ld-2J/J (Stock No. 002225) at The Jackson Laboratory in 1995. It was backcrossed a minimum of five generations to C57BL/10J in the laboratory of Dr. Wayne Frankel and Dr. Verity Letts and donated to the Repository in 2008.

Related Strains

Strains carrying other alleles of Cacna1a

008816	B6.129S7-Cacna1atm1Hzo/J
008815	B6.129S7-Cacna1atm2Hzo/J
008683	B6.129S7-Cacna1atm3Hzo/J
008622	B6.C3Bir-Cacna1atg-4J/LetJ
000566	B6.Cg-Os +/+ Cacna1atg-la/J
000544	B6.D2-Cacna1atg/J
005520	B6;CByJ-Cacna1atg-6J/J

View Strains carrying other alleles of Cacna1a     (7 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Cacna1a^Tg-5J/Cacna1a⁺

        B10.Cg-Cacna1a^Tg-5J

• behavior/neurological phenotype
• ataxia
  • gait is shaky and hindlimbs are splayed laterally from body   (MGI Ref ID J:137816)
• nervous system phenotype
• abnormal Purkinje cell morphology
  • Purkinje cell arbor is reduced in complexity and in overall dendritic mass   (MGI Ref ID J:137816)
• • abnormal Purkinje cell dendrite morphology
    • tips of distal dendrites have an abnormal serpentine-like appearance   (MGI Ref ID J:137816)
    • shafts of dendrites exhibit a thickening in the upper molecular layer   (MGI Ref ID J:137816)
• abnormal axon morphology
  • axonal swelling is observed in Purkinje cells   (MGI Ref ID J:137816)
• abnormal nervous system electrophysiology
  • calcium channel voltage activation and inactivation is shifted to lower voltages   (MGI Ref ID J:137816)

Cacna1a^Tg-5J/Cacna1a^Tg-5J

        B10.Cg-Cacna1a^Tg-5J

• mortality/aging
• complete preweaning lethality
  • on the B10 genetic background, no homozygotes are produced from heterozygote x heterozygote matings no homozygotes are produced from heterozygote x heterozygote matings   (MGI Ref ID J:137816)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Cacna1a^Tg-5J/Cacna1a^Tg-5J

        involves: BALB/cByJ * C57BL/10J

• mortality/aging
• partial preweaning lethality
  • only 3% of homozygotes are produced from heterozygote x heterozygote matings only 3% of homozygotes are produced from heterozygote x heterozygote matings   (MGI Ref ID J:137816)
• premature death
  • homozygotes do not live beyond 6 weeks of age   (MGI Ref ID J:137816)
• behavior/neurological phenotype
• ataxia
  • homozygotes are severely ataxic   (MGI Ref ID J:137816)
• growth/size phenotype
• decreased body size
  • runted   (MGI Ref ID J:137816)

View Research Applications

Research Applications

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

Cell Biology Research
Channel and Transporter Defects
      calcium

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
      Purkinje cell defect
Channel and Transporter Defects
      calcium

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cacna1aTg-5J
Allele Name		tottering 5 Jackson
Allele Type		Spontaneous
Strain of Origin		B10.M-H2f/nMob Fmn1ld-2J/J
Gene Symbol and Name		Cacna1a, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Chromosome		8
Gene Common Name(s)		APCA; BI; BccA1; CACNL1A4; CAV2.1; Ccha1a; EA2; FHM; HPCA; MHP; MHP1; SCA6; alpha1A; calcium channel alpha 1a; la; leaner; neuroscience mutagenesis facility, 352; nmf352; rbA-1; rkr; rocker; tg; tottering;
Molecular Note		A G to A substitution at nucleotide 3755 results in a change from arginine to glutamine. [MGI Ref ID J:137816]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Miki T; Zwingman TA; Wakamori M; Lutz CM; Cook SA; Hosford DA; Herrup K; Fletcher CF; Mori Y; Frankel WN; Letts VA. 2008. Two novel alleles of tottering with distinct Ca(v)2.1 calcium channel neuropathologies. Neuroscience 155(1):31-44. [PubMed: 18597946]  [MGI Ref ID J:137816]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes. On the C57BL/10J background, homozygous mice die by before birth.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Mouse Mutant Resource collection.

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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.

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