Overview

Also Known As:α₁3.2-, Cav3.2-

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.

Donating Investigator

Kevin Campbell, University of Iowa

Genetic overview

Genetic Background	Generation
	N6+pN1F3 (2021-04-02 00:00:00)

Cacna1h^tm1Kcam

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cacna1h	calcium channel, voltage-dependent, T type, alpha 1H subunit

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Research Applications

Cardiovascular Research
Developmental Biology Research

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Base Price

Starting at:

$278.00 Domestic price for female 4-week

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Details

Detailed 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 Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):1416-8PubMed: 14631046 MGI: J:86616

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Genetics

Cacna1h^tm1Kcam

Allele Symbol: Cacna1h^tm1Kcam

Allele Name	targeted mutation 1, Kevin P Campbell
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	alpha13.2^-; Cav3.2^-
Gene Symbol and Name	Cacna1h, calcium channel, voltage-dependent, T type, alpha 1H subunit
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	17
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.
Mutations Made By	Kevin Campbell, University of Iowa

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cardiovascular Research
- Vascular Defects
Developmental Biology Research
- Growth Defects
  - Growth Defects (homozygous)

Mammalian Phenotype Terms by Genotype

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

Genotype: Cacna1h^tm1Kcam/Cacna1h^tm1Kcam
involves: 129S1/Sv * 129X1/SvJ * ICR

behavior/neurological phenotype

abnormal vocalization
- mice emit an intermittent, high-pitched chirping sound

skeleton phenotype

abnormal tracheal cartilage morphology
- Normal - however, cartilage ring pattern in the bronchi, cricoid cartilage and cartilages from the xiphistemum, ear, nose and articular cartilage are normal
- mean number of disrupted cartilaginous rings is around 9.95
- cartilaginous rings of the trachea are frequently disrupted anteriorly, resembling an arch missing its keystone, thus collapsing the transverse diameter of the tracheal airway
- 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

abnormal cartilage development
- marker analysis indicates that condensation of chondroprogenitor cells in the trachea is disrupted
- embryonic limb bud mesenchymal cells undergo chondrogenic differentiation in cell culture to a less extent than wild-type mesenchymal cells

respiratory system phenotype

abnormal tracheal cartilage morphology
- 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
- mean number of disrupted cartilaginous rings is around 9.95
- Normal - however, cartilage ring pattern in the bronchi, cricoid cartilage and cartilages from the xiphistemum, ear, nose and articular cartilage are normal
- cartilaginous rings of the trachea are frequently disrupted anteriorly, resembling an arch missing its keystone, thus collapsing the transverse diameter of the tracheal airway

trachea stenosis
- tracheas are narrow and elliptically shaped, with the long axis oriented in the anterior-posterior direction

Genotype: Cacna1h^tm1Kcam/Cacna1h^tm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

muscle phenotype

increased vasoconstriction
- vessels in the heart and coronary arterioles are constitutively contracted
- isolated coronary arteries show normal contractile responses but show reduced relaxation in response to acetylcholine and ntiroprusside

abnormal myocardial fiber morphology
- focal myocardial fibrosis

nervous system phenotype

abnormal channel response
- the low voltage-activated calcium current (I_T is significantly diminished in dorsal root ganglia neurons, however no difference in the high voltage-activated calcium currents

cardiovascular system phenotype

abnormal cardiovascular system morphology

abnormal arteriole morphology
- exhibit constitutively constricted coronary arterioles

abnormal blood vessel morphology
- vessels in the heart have irregular spiral shapes

cardiac fibrosis
- exhibit progressive cardiac fibrosis starting at 10 weeks of age; hearts show large areas of fibrosis, necrosis, and lymphoctye infiltration

increased vasoconstriction
- vessels in the heart and coronary arterioles are constitutively contracted
- isolated coronary arteries show normal contractile responses but show reduced relaxation in response to acetylcholine and ntiroprusside

abnormal myocardial fiber morphology
- focal myocardial fibrosis

growth/size/body region phenotype

decreased body size
- both males and females are smaller

References

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):1416-8PubMed: 14631046 MGI: J:86616

Additional - Cacna1h^tm1Kcam related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Cacna1h
- Standard PCR:Cacna1h
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintained as a live colony, homozygotes or heterozygotes may be bred.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the α₁3.2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #013770 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Cacna1h<tm1Kcam>

Related Products and Services

Frozen Mouse Embryo	B6;129-Cacna1h<tm1Kcam>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129-Cacna1h<tm1Kcam>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129-Cacna1h<tm1Kcam>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129-Cacna1h<tm1Kcam>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

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.

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

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:α13.2-, Cav3.2-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Cacna1htm1Kcam

Allele Symbol: Cacna1htm1Kcam

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cacna1htm1Kcam/Cacna1htm1Kcaminvolves: 129S1/Sv * 129X1/SvJ * ICR

behavior/neurological phenotype

skeleton phenotype

respiratory system phenotype

Genotype: Cacna1htm1Kcam/Cacna1htm1Kcaminvolves: 129S1/Sv * 129X1/SvJ * C57BL/6J

muscle phenotype

nervous system phenotype

cardiovascular system phenotype

growth/size/body region phenotype

References

Additional - Cacna1htm1Kcam related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:α₁3.2-, Cav3.2-

Cacna1h^tm1Kcam

Allele Symbol: Cacna1h^tm1Kcam

Genotype: Cacna1h^tm1Kcam/Cacna1h^tm1Kcam
involves: 129S1/Sv * 129X1/SvJ * ICR

Genotype: Cacna1h^tm1Kcam/Cacna1h^tm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Additional - Cacna1h^tm1Kcam related