Strain Name:

B6;129-Cacna1htm1Kcam/J

Stock Number:

013770

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Availability:

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These Cacna1h knock-out mice have constitutively constricted coronary arterioles and focal myocardial fibrosis. This strain may be useful in studies of coronary artery function and disease.

Description

Strain Information

Former Names B6.129-Cacna1htm1Kcam/J    (Changed: 28-JUN-12 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   26-OCT-11
Specieslaboratory mouse
GenerationN7+F7 (10-DEC-13)
Generation Definitions
 
Donating Investigator Kevin Campbell,   University of Iowa

Description
Homozygous Cacna1h (calcium channel, voltage-dependent, T type, alpha 1H subunit; also called α1 3.2) targeted mutant mice have constitutively constricted coronary arterioles and focal myocardial fibrosis. Isolated arteries show normal contractile responses but reduced relaxation in response to acetylcholine and nitroprusside. Diffuse areas of cardiac fribrosis are observed in ventricular walls from 10-week old mice, but not those of wildtype mice. At 1 year of age, their hearts have a more severe cardiac pathology, including larger areas of fibrosis, necrosis and lymphocyte infiltration. Homozygotes are smaller than littermate controls. Heterozygotes do not show any abnormalities. Northern and/or Western blot analysis of brain, testis and dorsal root ganglion tissues confirms the loss of RNA and protein in mice. This strain may be useful in studies of coronary artery function and disease.

Development
Exon 6, encoding amino acid residues 216-267, was replaced with a loxP-flanked neomycin resistance cassette in (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. The donating investigator reports that mutant mice were backcrossed to C57BL/6 mice for six generations prior to sending to The Jackson Laboratory Repository (see SNP notes below). Upon arrival, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with markers covering all 19 chromosomes and the X chromosome, was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed markers on Chromosome 4 and 6, and two markers on chromosome 8 that were not fixed for C57BL/6 allele-type (e.g.: still segregating for 129X1/129S1 allele-type markers). These data suggests an incomplete backcross.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Epilepsy, Childhood Absence, Susceptibility to, 6; ECA6   (CACNA1H)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Cacna1htm1Kcam/Cacna1htm1Kcam

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
  • cardiovascular system phenotype
  • abnormal cardiovascular system morphology   (MGI Ref ID J:86616)
    • abnormal blood vessel morphology
      • vessels in the heart have irregular spiral shapes   (MGI Ref ID J:86616)
      • abnormal arteriole morphology
        • exhibit constitutively constricted coronary arterioles   (MGI Ref ID J:86616)
    • abnormal myocardial fiber morphology
      • focal myocardial fibrosis   (MGI Ref ID J:86616)
    • cardiac fibrosis
      • exhibit progressive cardiac fibrosis starting at 10 weeks of age; hearts show large areas of fibrosis, necrosis, and lymphoctye infiltration   (MGI Ref ID J:86616)
  • increased vasoconstriction
    • vessels in the heart and coronary arterioles are constitutively contracted   (MGI Ref ID J:86616)
    • isolated coronary arteries show normal contractile responses but show reduced relaxation in response to acetylcholine and ntiroprusside   (MGI Ref ID J:86616)
  • growth/size/body phenotype
  • decreased body size
    • both males and females are smaller   (MGI Ref ID J:86616)
  • nervous system phenotype
  • abnormal channel response
    • the low voltage-activated calcium current (IT is significantly diminished in dorsal root ganglia neurons, however no difference in the high voltage-activated calcium currents   (MGI Ref ID J:86616)
  • muscle phenotype
  • abnormal myocardial fiber morphology
    • focal myocardial fibrosis   (MGI Ref ID J:86616)
  • increased vasoconstriction
    • vessels in the heart and coronary arterioles are constitutively contracted   (MGI Ref ID J:86616)
    • isolated coronary arteries show normal contractile responses but show reduced relaxation in response to acetylcholine and ntiroprusside   (MGI Ref ID J:86616)
  • homeostasis/metabolism phenotype
  • cardiac fibrosis
    • exhibit progressive cardiac fibrosis starting at 10 weeks of age; hearts show large areas of fibrosis, necrosis, and lymphoctye infiltration   (MGI Ref ID J:86616)

Cacna1htm1Kcam/Cacna1htm1Kcam

        involves: 129S1/Sv * 129X1/SvJ * ICR
  • behavior/neurological phenotype
  • abnormal vocalization
    • mice emit an intermittent, high-pitched chirping sound   (MGI Ref ID J:208830)
  • respiratory system phenotype
  • abnormal tracheal cartilage morphology
    • cartilaginous rings of the trachea are frequently disrupted anteriorly, resembling an arch missing its keystone, thus collapsing the transverse diameter of the tracheal airway   (MGI Ref ID J:208830)
    • mean number of disrupted cartilaginous rings is around 9.95   (MGI Ref ID J:208830)
    • abnormal tracheal rings are seen at both E14.5 and P1 and almost all the cartilage rings are disrupted at these times, indicating congenital tracheal malformations   (MGI Ref ID J:208830)
    • however, cartilage ring pattern in the bronchi, cricoid cartilage and cartilages from the xiphistemum, ear, nose and articular cartilage are normal   (MGI Ref ID J:208830)
  • trachea stenosis
    • tracheas are narrow and elliptically shaped, with the long axis oriented in the anterior-posterior direction   (MGI Ref ID J:208830)
  • skeleton phenotype
  • abnormal cartilage development
    • embryonic limb bud mesenchymal cells undergo chondrogenic differentiation in cell culture to a less extent than wild-type mesenchymal cells   (MGI Ref ID J:208830)
    • marker analysis indicates that condensation of chondroprogenitor cells in the trachea is disrupted   (MGI Ref ID J:208830)
  • abnormal tracheal cartilage morphology
    • cartilaginous rings of the trachea are frequently disrupted anteriorly, resembling an arch missing its keystone, thus collapsing the transverse diameter of the tracheal airway   (MGI Ref ID J:208830)
    • mean number of disrupted cartilaginous rings is around 9.95   (MGI Ref ID J:208830)
    • abnormal tracheal rings are seen at both E14.5 and P1 and almost all the cartilage rings are disrupted at these times, indicating congenital tracheal malformations   (MGI Ref ID J:208830)
    • however, cartilage ring pattern in the bronchi, cricoid cartilage and cartilages from the xiphistemum, ear, nose and articular cartilage are normal   (MGI Ref ID J:208830)
View Research Applications

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

Cardiovascular Research
Vascular Defects

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Cacna1htm1Kcam
Allele Name targeted mutation 1, Kevin P Campbell
Allele Type Targeted (Null/Knockout)
Common Name(s) Cav3.2-; alpha13.2-;
Mutation Made By Kevin Campbell,   University of Iowa
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Cacna1h, calcium channel, voltage-dependent, T type, alpha 1H subunit
Chromosome 17
Gene Common Name(s) CACNA1HB; Cav3.2; ECA6; EIG6; T-type Cav3.2; alpha13.2; mKIAA1120;
Molecular Note Exon 6, which encodes residues 216 through 267, was replaced with a floxed neo cassette inserted by homologous recombination. Transcript was undetected by Northern blot analysis of RNA obtained from homozygous mutant testes. Similarly, Western blot analysis of extracts from homozygous mutant brain tissue indicated an absence of normal protein. [MGI Ref ID J:86616]

Genotyping

Genotyping Information

Genotyping Protocols

Cacna1htm1Kcam, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Cacna1htm1Kcam related

Aptel H; Hilaire C; Pieraut S; Boukhaddaoui H; Mallie S; Valmier J; Scamps F. 2007. The Cav3.2/alpha1H T-type Ca2+ current is a molecular determinant of excitatory effects of GABA in adult sensory neurons. Mol Cell Neurosci 36(2):293-303. [PubMed: 17716912]  [MGI Ref ID J:126811]

Becker AJ; Pitsch J; Sochivko D; Opitz T; Staniek M; Chen CC; Campbell KP; Schoch S; Yaari Y; Beck H. 2008. Transcriptional upregulation of Cav3.2 mediates epileptogenesis in the pilocarpine model of epilepsy. J Neurosci 28(49):13341-53. [PubMed: 19052226]  [MGI Ref ID J:142918]

Chen CC; Lamping KG; Nuno DW; Barresi R; Prouty SJ; Lavoie JL; Cribbs LL; England SK; Sigmund CD; Weiss RM; Williamson RA; Hill JA; Campbell KP. 2003. Abnormal coronary function in mice deficient in alpha1H T-type Ca2+ channels. Science 302(5649):1416-8. [PubMed: 14631046]  [MGI Ref ID J:86616]

Chen WK; Liu IY; Chang YT; Chen YC; Chen CC; Yen CT; Shin HS; Chen CC. 2010. Ca(v)3.2 T-type Ca2+ channel-dependent activation of ERK in paraventricular thalamus modulates acid-induced chronic muscle pain. J Neurosci 30(31):10360-8. [PubMed: 20685979]  [MGI Ref ID J:166291]

Choi S; Na HS; Kim J; Lee J; Lee S; Kim D; Park J; Chen CC; Campbell KP; Shin HS. 2007. Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels. Genes Brain Behav 6(5):425-31. [PubMed: 16939637]  [MGI Ref ID J:137286]

Cui J; Ivanova E; Qi L; Pan ZH. 2012. Expression of CaV3.2 T-type Ca(2)(+) channels in a subpopulation of retinal type-3 cone bipolar cells. Neuroscience 224:63-9. [PubMed: 22909426]  [MGI Ref ID J:192487]

Figueroa XF; Chen CC; Campbell KP; Damon DN; Day KH; Ramos S; Duling BR. 2007. Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone? Am J Physiol Heart Circ Physiol 293(3):H1371-83. [PubMed: 17513486]  [MGI Ref ID J:126105]

Howitt L; Kuo IY; Ellis A; Chaston DJ; Shin HS; Hansen PB; Hill CE. 2013. Chronic deficit in nitric oxide elicits oxidative stress and augments T-type calcium-channel contribution to vascular tone of rodent arteries and arterioles. Cardiovasc Res 98(3):449-57. [PubMed: 23436820]  [MGI Ref ID J:211448]

Huang Z; Lujan R; Kadurin I; Uebele VN; Renger JJ; Dolphin AC; Shah MM. 2011. Presynaptic HCN1 channels regulate Cav3.2 activity and neurotransmission at select cortical synapses. Nat Neurosci 14(4):478-86. [PubMed: 21358644]  [MGI Ref ID J:172304]

Jacus MO; Uebele VN; Renger JJ; Todorovic SM. 2012. Presynaptic CaV3.2 Channels Regulate Excitatory Neurotransmission in Nociceptive Dorsal Horn Neurons. J Neurosci 32(27):9374-82. [PubMed: 22764245]  [MGI Ref ID J:185954]

Latham JR; Pathirathna S; Jagodic MM; Joo Choe W; Levin ME; Nelson MT; Yong Lee W; Krishnan K; Covey DF; Todorovic SM; Jevtovic-Todorovic V. 2009. Selective T-type calcium channel blockade alleviates hyperalgesia in ob/ob mice. Diabetes 58(11):2656-65. [PubMed: 19651818]  [MGI Ref ID J:154387]

Li Y; Wang F; Zhang X; Qi Z; Tang M; Szeto C; Li Y; Zhang H; Chen X. 2012. beta-Adrenergic stimulation increases Cav3.1 activity in cardiac myocytes through protein kinase A. PLoS One 7(7):e39965. [PubMed: 22808078]  [MGI Ref ID J:189633]

Lin SS; Tzeng BH; Lee KR; Smith RJ; Campbell KP; Chen CC. 2014. Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage. Proc Natl Acad Sci U S A 111(19):E1990-8. [PubMed: 24778262]  [MGI Ref ID J:208830]

Rose KE; Lunardi N; Boscolo A; Dong X; Erisir A; Jevtovic-Todorovic V; Todorovic SM. 2013. Immunohistological demonstration of CaV3.2 T-type voltage-gated calcium channel expression in soma of dorsal root ganglion neurons and peripheral axons of rat and mouse. Neuroscience 250:263-74. [PubMed: 23867767]  [MGI Ref ID J:207044]

Thuesen AD; Andersen H; Cardel M; Toft A; Walter S; Marcussen N; Jensen BL; Bie P; Hansen PB. 2014. Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo. Am J Physiol Renal Physiol 307(4):F445-52. [PubMed: 24966091]  [MGI Ref ID J:213554]

Tzeng BH; Chen YH; Huang CH; Lin SS; Lee KR; Chen CC. 2012. The Ca(v)3.1 T-type calcium channel is required for neointimal formation in response to vascular injury in mice. Cardiovasc Res 96(3):533-42. [PubMed: 22886848]  [MGI Ref ID J:210079]

Wang R; Lewin GR. 2011. The Cav3.2 T-type calcium channel regulates temporal coding in mouse mechanoreceptors. J Physiol 589(Pt 9):2229-43. [PubMed: 21486775]  [MGI Ref ID J:184663]

Zheng H; Park KS; Koh SD; Sanders KM. 2014. Expression and function of a T-type Ca2+ conductance in interstitial cells of Cajal of the murine small intestine. Am J Physiol Cell Physiol 306(7):C705-13. [PubMed: 24477235]  [MGI Ref ID J:210187]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, homozygotes or heterozygotes may be bred.
Mating SystemHomozygote x Homozygote         (Female x Male)   26-OCT-11
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHomozygous for Cacna1htm1Kcam  
Price per Pair (US dollars $)Pair Genotype
$399.80Homozygous for Cacna1htm1Kcam x Homozygous for Cacna1htm1Kcam  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHomozygous for Cacna1htm1Kcam  
Price per Pair (US dollars $)Pair Genotype
$519.80Homozygous for Cacna1htm1Kcam x Homozygous for Cacna1htm1Kcam  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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