Overview

Also Known As:mAKAP^fl

These mAKAP6^fl mutant mice possess loxP sites flanking exon 9 of the A kinase (PRKA) anchor protein 6 (Akap6) gene, a scaffold protein located in the nuclear envelope of striated myocytes. This strain may be useful for studying cardiac hypertrophy and heart failure.

Donating Investigator

Michael Kapiloff, Stanford University

Genetic overview

Genetic Background	Generation

Akap6^tm1.1Mskf

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Akap6	A kinase (PRKA) anchor protein 6

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Research Applications

Research Tools

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Details

Detailed Description

These mAKAP6^fl mutant mice possess loxP sites flanking exon 9 of the A kinase (PRKA) anchor protein 6 (Akap6) gene. Akap6 is a scaffold protein located in the nuclear envelope of striated myocytes; it functions as nodal organizer of hypertrophic signaling. Mice that are homozygous for this allele are viable, fertile, and normal in size. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 9 deleted in the cre-expressing tissues. This strain may be useful for studying cardiac hypertrophy and heart failure.

When bred to mice carrying Tg(Myh6-cre/Esr1*)1Jmk, tamoxifen-induced Cre-mediated recombination and stress by transverse aortic constriction results in a cardiac protective effect when compared to controls subjected to the same regime.

Development

The targeting vector contains a FRT-flanked neomycin cassette followed by a loxP site upstream exon 9 and loxP downstream of exon 9. The targeting vector was introduced to unspecified C57BL/6-derived embryonic stem (ES) cells. The neomycin resistance cassette was subsequently excised by crossing to
B6;SJL-Tg(ACTFLPe)9205Dym/J mice, leaving exon 9 flanked by loxP sites. Progeny were crossed to remove the FLPe-expressing transgene. This strain was backcrossed to C57BL/6 for an unknown number generations by the donating investigator. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Suggestions

Wild-type littermate

Additional Information

Considerations for Choosing Controls

Selected References

Kritzer MD; Li J; Passariello CL; Gayanilo M; Thakur H; Dayan J; Dodge-Kafka K; Kapiloff MS. 2014. The scaffold protein muscle A-kinase anchoring protein beta orchestrates cardiac myocyte hypertrophic signaling required for the development of heart failure. Circ Heart Fail 7(4):663-72PubMed: 24812305 MGI: J:214288

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Genetics

Akap6^tm1.1Mskf

Allele Symbol: Akap6^tm1.1Mskf

Allele Name	targeted mutation 1.1, Michael S Kapiloff
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	mAKAP^fl
Gene Symbol and Name	Akap6, A kinase (PRKA) anchor protein 6
Gene Synonym(s)
Strain of Origin	C57BL/6
Chromosome	12
Molecular Note	The targeting vector contains a FRT-flanked neomycin cassette followed by a loxP site upstream exon 9 and loxP downstream of exon 9. Flpe mediated recombination removed the FRT-flanked neo cassette leaving exon 9 floxed.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Cardiovascular Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

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

Genotype: Akap6^tm1.1Mskf/Akap6^tm1.1Mskf A1cf^{Tg(Myh6-cre/Esr1)1Jmk}/A1cf⁺
involves: C57BL/6 FVB/N * SJL

cellular phenotype

increased cardiomyocyte apoptosis
- following a long term LT-TAC, mice administered tamoxifen exhibit increased apoptosis, but 75% less myocardial apoptosis as compared controls subjected to the same regime

growth/size/body region phenotype

increased heart left atrium weight
- to the same regime
- following cardiac stress by long term transverse aortic constriction (LT-TAC), mice administered tamoxifen exhibit increased left atrial weight (35%) as compared controls undergoing a sham procedure, but less than the increase (50%) in controls subjected to the same regime

heart left ventricle hypertrophy
- following a long term (LT) TAC, mice administered tamoxifen die as a result of congenital heart failure, but exhibit greater survival than controls subjected to the same regime (6% vs 29%) and do not exhibit pulmonary edema

increased left ventricle weight
- following a LT-TAC, mice administered tamoxifen die as a result of congenital heart failure, but exhibit greater survival than controls subjected to the same regime (6% vs 29%) and do not exhibit pulmonary edema

muscle phenotype

heart left ventricle hypertrophy
- following a long term (LT) TAC, mice administered tamoxifen die as a result of congenital heart failure, but exhibit greater survival than controls subjected to the same regime (6% vs 29%) and do not exhibit pulmonary edema

increased cardiomyocyte apoptosis
- following a long term LT-TAC, mice administered tamoxifen exhibit increased apoptosis, but 75% less myocardial apoptosis as compared controls subjected to the same regime

enlarged myocardial fiber
- following 2 weeks of TAC or isoproterenol infusion, left venticle (LV) myocytes from mice administered tamoxifen exhibit an increase in cross section area, but to a much lessor extent than controls subjected to the same regime

cardiovascular system phenotype

abnormal heart ventricles weight
- following a 5 week swimming regime, mice administered tamoxifen exhibit an increase in biventricular weight gain, but to a lessor extent than controls subjected to the same regime (13% vs 5%)
- following 2 weeks of cardiac stress by transverse aortic constriction (TAC) or isoproterenol infusion, mice administered tamoxifen exhibit increased biventricular weight, but to a much lessor extent than controls subjected to the same regime

enlarged myocardial fiber
- following 2 weeks of TAC or isoproterenol infusion, left venticle (LV) myocytes from mice administered tamoxifen exhibit an increase in cross section area, but to a much lessor extent than controls subjected to the same regime

increased left ventricle weight
- following a LT-TAC, mice administered tamoxifen die as a result of congenital heart failure, but exhibit greater survival than controls subjected to the same regime (6% vs 29%) and do not exhibit pulmonary edema

thick ventricular wall
- following 2 weeks of TAC or isoproterenol infusion, mice administered tamoxifen exhibit increased left ventricular (LV) wall thickness, but to a much lessor extent than controls subjected to the same regime

decreased heart rate
- following a 5 week swimming regime, mice administered tamoxifen exhibit lower heart rate than controls subjected to the same regime

increased heart left atrium weight
- to the same regime
- following cardiac stress by long term transverse aortic constriction (LT-TAC), mice administered tamoxifen exhibit increased left atrial weight (35%) as compared controls undergoing a sham procedure, but less than the increase (50%) in controls subjected to the same regime

increased cardiomyocyte apoptosis
- following a long term LT-TAC, mice administered tamoxifen exhibit increased apoptosis, but 75% less myocardial apoptosis as compared controls subjected to the same regime

cardiac interstitial fibrosis
- following a long term LT-TAC, mice administered tamoxifen exhibit increased collagen deposistion, but 78% less collagen deposition as compared controls subjected to the same regime

heart left ventricle hypertrophy
- following a long term (LT) TAC, mice administered tamoxifen die as a result of congenital heart failure, but exhibit greater survival than controls subjected to the same regime (6% vs 29%) and do not exhibit pulmonary edema

References

Kritzer MD; Li J; Passariello CL; Gayanilo M; Thakur H; Dayan J; Dodge-Kafka K; Kapiloff MS. 2014. The scaffold protein muscle A-kinase anchoring protein beta orchestrates cardiac myocyte hypertrophic signaling required for the development of heart failure. Circ Heart Fail 7(4):663-72PubMed: 24812305 MGI: J:214288

Additional - Akap6^tm1.1Mskf related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Generic Cre Probe
- Probe:Generic FLP
- Standard PCR:Akap6
- Standard PCR:Generic Neo
- Probe:Generic Neo
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the mAKAP^fl mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37540 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:mAKAPfl

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Akap6tm1.1Mskf

Allele Symbol: Akap6tm1.1Mskf

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Akap6tm1.1Mskf/Akap6tm1.1Mskf A1cfTg(Myh6-cre/Esr1*)1Jmk/A1cf+involves: C57BL/6 * FVB/N * SJL

cellular phenotype

growth/size/body region phenotype

muscle phenotype

cardiovascular system phenotype

References

Additional - Akap6tm1.1Mskf related

Genotyping Protocols

Breeding Considerations

Mating System

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

Also Known As:mAKAP^fl

Akap6^tm1.1Mskf

Allele Symbol: Akap6^tm1.1Mskf

Genotype: Akap6^tm1.1Mskf/Akap6^tm1.1Mskf A1cf^{Tg(Myh6-cre/Esr1)1Jmk}/A1cf⁺
involves: C57BL/6 FVB/N * SJL

Additional - Akap6^tm1.1Mskf related