Strain Detail Sheet

Strain Name:
STOCK Cacna1ctm1Msmg/Mmucd
Stock Number:
050631-UCD
Citation ID:
RRID:MMRRC_050631-UCD
Other Names:
CaV1.2 Ser1928Ala

Strain Information

Gene Details

Cacna1ctm1Msmg
Name: calcium channel, voltage-dependent, L type, alpha 1C subunit; targeted mutation 1, Sven Moosmang
Synonyms: S1928A KI
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 6
Alteration at locus: Knock-In
Cacna1c
Name: calcium channel, voltage-dependent, L type, alpha 1C subunit
Synonyms: D930026N18Rik, (alpha)1 subunit, Cchl1a1, Cav1.2, L-type Cav1.2
Type: Gene
Species: Mouse
Chromosome: 6
Alteration at locus: Knock-In
NCBI: 12288
HGNC: HGNC:1390
Homologene: 55484
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Genetic Alterations

Serine-to-alanine substitution at position 1927 along with insertion of extra base pairs into the adjacent intronic region for genotyping.

HGVS nomenclature:

  • Genbank RefSeq - mRNA: NM_009781.4 (longest of many isoforms)
  • Genbank RefSeq, protein: NP_033911.2
  • Variant, nucleic acid level: c.5779T>G
  • Variant, amino acid level, predicted: p.Ser1927Ala

Note: The literature refers to this variant as S1928A, which is based on phosphorylation work by the Catterall group (PMID:17053072 and PMID:8756695). The latter report used the cDNA sequence from rabbit heart (PMID:2474130) to identify the sequence position of the prominent phospho-peptide as Ser1928. Franz Hofmann's group (Donor, PMID:18829456) cloned exon 44-47 from a 129/Sv cDNA library and identified the sequence accordingly as S1928.
Genotype Determination
Genotyping Protocol
ES Cell Line
R1 derived from (129X1/SvJ x 129S1/Sv)F1-Kitl+

Strain Description

Phenotype
Although derived originally with the hypothesis that cardiac cell calcium currents would be blunted by preventing phosphorylation of the voltage-gated calcium channel CaV1.2 at its C-terminal tail via adrenergic signaling, no such phenotype was observed in these CaV1.2 Ser1928Ala mice. Surprisingly, subsequent investigations showed that calcium currents are indeed inhibited relative to WT, but only in other excitable tissues, and especially in brain and smooth muscle cells, indicating that distinct modes of calcium channel regulation must exist between these organ systems. Furthermore, adrenergic regulation of CaV1.2 by C-tail phosphorylation is now implicated in the regulation of important physiological functions dependent on affected excitable tissues, such as neuronal signaling underlying attention, learning, and memory behaviors, and smooth muscle cell signaling involved in diabetes.
Mammalian Phenotype Terms
Allelic Composition: (Genetic Background: )
MeSH Terms
  • Alanine/chemistry
  • Animals
  • Calcium Channels, L-Type/chemistry
  • Calcium Channels, L-Type/genetics
  • Calcium Channels, L-Type/metabolism
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Echocardiography
  • Electrophysiology
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Mutation
  • Myocytes, Cardiac/metabolism
  • Phosphorylation
  • Receptors, Adrenergic, beta/metabolism
  • Serine/chemistry
Strain Development
To construct the targeting vector, a 7.4-kb fragment containing exons 44–47 of Cacna1c was isolated from129/Sv mouse genomic DNA. The targeting vector included a 1.2-kb short arm and 6.2-kb long arm with PGK-neo and the thymidine kinase gene (tk) flanked by two loxP sites. The 3’-side long arm contained exon 45 with the phosphorylation site, serine 1928, mutated to alanine. All mutation procedures were carried out by overlap PCR mutagenesis. The targeting construct was electroporated into R1 ES cells. Positive clones were identified by PCR and confirmed by Southern blot using an outer probe. Two positive clones were transfected with a Cre-expressing plasmid to delete the neo/tk marker genes. Five clones with the deletion event were injected in C57BL/6 blastocysts, and chimeras were crossed to C57BL/6 mice. Heterozygous mice were bred to produce homozygotes. The intercross of heterozygotes resulted in the production of wild-type, heterozygous, and homozygous offspring at almost the expected Mendelian ratio (125:215:88). For all analyses, mice with 129/Sv and C57BL/6hybrid genetic background (Cav1.2S1928A-129B6F2) were used.
Suggested Control Mice
B6129SF1/J (JAX Strain #101043)

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.

Research Applications

  • Cardiovascular
  • Diabetes
  • Neurobiology

Strain Origin

Donor
Franz Hofmann, M.D., Technische Universität.
Johannes Hell, Ph.D., UC Davis.
Primary Reference

Lemke T, Welling A, Christel CJ, Blaich A, Bernhard D, Lenhardt P, Hofmann F, Moosmang S. Unchanged beta-adrenergic stimulation of cardiac L-type calciumchannels in Ca v 1.2 phosphorylation site S1928A mutant mice. J Biol Chem. 2008Dec 12;283(50):34738-44. doi: 10.1074/jbc.M804981200. Epub 2008 Sep 30. (Medline PMID: 18829456)

Colony and Husbandry Information

Health Status Report

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.

Appearance

Coat Color
Agouti
Eye
Black
Other
Donor communication: "This mouse model has become increasingly important for investigations in neuroscience and the regulation of diabetes signaling. Our laboratory also has as-yet unpublished findings that we anticipate will generate further interest in this model..."

Breeding

MMRRC Breeding System
Random intra-strain mating
Generation

N1 (B6129SF1/J - JAX Strain #101043)

Overall Breeding Performance
Excellent

Reproductive Statistics

Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Greater than 12 months Greater than 12 months
Average litter size
7-9
Recommended wean age
3 Weeks
Average Pups Weaned
5-9

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

Conditions of Distribution

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*		 Units Notes
050631-UCD-SPERM Cryo-preserved spermatozoa $546.25 / $869.88
Non-Profit / For-Profit		 Aliquot Approximate quantity3
050631-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / $7,650.23
Non-Profit / For-Profit		 Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.