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Strain Name:
B6SJL-Tg(Myh6-MYL3*)#Dsc/Mmjax
Stock Number:
075951-JAX
Citation ID:
RRID:MMRRC_075951-JAX
Other Names:
Δ43 ELC

Strain Information

QUALITY CONTROL OF B6SJL-Tg(Myh6-MYL3*)#Dsc/Mmjax  |  The Jackson Laboratory
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3n.d.
Genetic backgroundn.d.
Viability of genotypes available for distributionn.d.
Specific Pathogen- Status n.d.
Recoverability of cryopreserved sperm/embryos4 n.d.
Gene or allele sequence3n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distributionn.d.
Fecundity/breeding performance n.d.

1 When indicated as verified ("YES"), then please note that information presented is to the best of our knowledge correct and up-to-date at the time of verification at the MMRRC Distribution Center; however, this information is subject to change due to breeding, maintenance, and other actions on the mouse strain at the MMRRC Distribution Center; direct any questions on this table to the MMRRC Distribution Center for this mouse stain.

2 If verification has not been performed (as indicated by "NO"), investigators may request specific verification testing for a fee. Requests should be submitted directly to the MMRRC Distribution Center assigned to the management, archiving, and distribution of the strain. A full listing of available testing and analytical services is available at https://www.mmrrc.org/about/services.php.

3 This information may or may not apply to each individual engineered allele (e.g., Cre, FlpO) present in the strain.

4 Recovery refers to thawing, in vitro fertilization (IVF), and/or embryo culture leading to live offspring.

Myh6
Name: myosin, heavy polypeptide 6, cardiac muscle, alpha
Synonyms: alpha myosin, Myhc-a, alpha cardiac MHC, cardiomyopathy, hypertrophic 1, Myhca, A830009F23Rik, alpha-MHC, alphaMHC
Type: Gene
Species: Mouse
Chromosome: 14
NCBI: 17888
HGNC: HGNC:7576
Homologene: 124414
MYL3
Name: myosin light chain 3
Type: Gene
Species: Homo sapiens (human)
Chromosome: 3
Tg(Myh6-MYL3*)#Dsc
Name: transgene insertion, Danuta Szczesna-Cordary
Synonyms: Tg-delta43, MYL3-delta43
Type: Transgene
Species: Multi-species
Chromosome: Unknown
Alteration at locus: Transgenic
Genetic Alterations

The cDNA encoding the wild-type human ventricular myosin essential light chain (ELC, NCBI accession no. NP_000249) and a 43-amino acid N-terminal truncation are under the control of the mouse alpha-myosin heavy chain promoter (Myh6), including the first two exons and part of the third. Following is the human MYL3 cDNA carrying 43bp deletion and a 630bp 3' untranslated region (UTR) from the human growth hormone (hGH) transcript. The truncated protein is similar in sequence to the short MYL3 present in skeletal muscle. Multiple lines were generated (L2, L4, L5, L7, L8, and L9), however, the pound symbol (#) is used when line is not specified and/or lines are pooled.

ES Cell Line
Not applicable
Phenotype
The Tg-Δ43 mouse line expresses a 43-amino-acid N-terminal truncation of the human ventricular essential light chain (ELC), driven by the cardiac-specific α-myosin heavy chain promoter. Although Δ43 partially replaces the endogenous mouse ELC, these mice:

  1. Do not develop pathological cardiomyopathy
  2. Exhibit age-progressive but physiological hypertrophy with preserved morphology, no fibrosis, and normal cardiac function.
  3. Contractility studies show unchanged maximal force and calcium sensitivity compared to wild type mice, while reduced rigor stiffness indicates that the missing N-terminal extension normally contributes to mechanical linkage between myosin and actin.

Mechanistically, deletion of the N-terminal ELC domain shifts myosin toward the super-relaxed (SRX) state, lowering ATP turnover and reducing actin-activated myosin ATPase activity. This SRX stabilization likely underlies the low-energy, compensatory hypertrophic growth of the Δ43 heart. Importantly, introducing Δ43 ELC into hypercontractile A57G mutant mice reverses hypertrophy and fibrosis and restores normal SRX regulation, suggesting that Δ43 functions as an energy-preserving brake on myosin activity and may hold therapeutic potential for treating hypercontractile sarcomeric mutations.
MeSH Terms
  • Actins/metabolism
  • Aging/physiology
  • Amino Acid Sequence
  • Animals
  • Calcium/metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Myocardial Contraction/physiology
  • Myocardium/cytology
  • Myocardium/metabolism
  • Myofibrils/metabolism
  • Myosin Light Chains/chemistry
  • Myosin Light Chains/genetics
  • Myosin Light Chains/metabolism
  • Myosins/metabolism
  • Protein Isoforms/chemistry
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Sequence Alignment
  • Amino Acid Substitution
  • Cardiomyopathy, Hypertrophic, Familial/etiology
  • Cardiomyopathy, Hypertrophic, Familial/genetics
  • Cardiomyopathy, Hypertrophic, Familial/physiopathology
  • Mice, Mutant Strains
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutant Proteins/chemistry
  • Mutant Proteins/genetics
  • Mutant Proteins/physiology
  • Myocardial Contraction/genetics
  • Myocardium/pathology
  • Myosin Light Chains/physiology
  • Papillary Muscles/pathology
  • Papillary Muscles/physiopathology
  • Peptide Fragments/chemistry
  • Peptide Fragments/genetics
  • Protein Conformation
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/genetics
  • Recombinant Proteins/metabolism
  • X-Ray Diffraction
  • Adenosine Diphosphate/genetics
  • Adenosine Diphosphate/metabolism
  • Adenosine Triphosphate/genetics
  • Adenosine Triphosphate/metabolism
  • Calcium
  • Kinetics
  • Myocardial Contraction
  • Papillary Muscles/metabolism
  • Phosphates/metabolism
  • Sequence Deletion
  • Biomechanical Phenomena
  • Excitation Contraction Coupling
  • Gene Deletion
  • Muscle Strength
  • Myocytes, Cardiac/metabolism
  • Sarcomeres/metabolism
  • Cardiomegaly/genetics
  • Cardiomegaly/metabolism
  • Cardiomegaly/pathology
  • Disease Models, Animal
  • Down-Regulation/physiology
  • Heart/physiology
  • Mitochondrial Proteins/metabolism
  • Mutation/genetics
  • Proteome/metabolism
  • Proteomics/methods
  • Up-Regulation/physiology
  • Ventricular Remodeling/genetics
  • Ventricular Remodeling/physiology
  • Cardiac Myosins/chemistry
  • Cardiac Myosins/metabolism
  • Myocardium/chemistry
  • Protein Multimerization
  • Swine
  • Cardiomegaly/physiopathology
  • Cardiomyopathy, Hypertrophic/genetics
  • Cardiomyopathy, Hypertrophic/metabolism
  • Cardiomyopathy, Hypertrophic/physiopathology
  • Echocardiography
  • Mutation
  • Cardiomyopathies/genetics
  • Cardiomyopathies/metabolism
  • Phosphorylation
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
  • Cardiovascular
  • Models for Human Disease
  • Research Tools
Donor
Danuta Szczesna-cordary, Ph.D., University of Miami Miller School of Medicine.
Primary Reference

Kazmierczak K, Xu Y, Jones M, Guzman G, Hernandez OM, Kerrick WG, Szczesna-Cordary D. The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction. J Mol Biol. 2009 Apr 3;387(3):706-25. doi: 10.1016/j.jmb.2009.02.006. Epub 2009 Feb 11. (Medline PMID: 19361417)

Muthu P, Wang L, Yuan CC, Kazmierczak K, Huang W, Hernandez OM, Kawai M, Irving TC, Szczesna-Cordary D. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction. FASEB J. 2011 Dec;25(12):4394-405. doi: 10.1096/fj.11-191973. Epub 2011 Sep 1. (Medline PMID: 21885653)

Wang L, Muthu P, Szczesna-Cordary D, Kawai M. Characterizations of myosin essential light chain's N-terminal truncation mutant Δ43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations. J Muscle Res Cell Motil. 2013 May;34(2):93-105. doi: 10.1007/s10974-013-9337-x. Epub 2013 Feb 9. (Medline PMID: 23397074)

Michael JJ, Gollapudi SK, Ford SJ, Kazmierczak K, Szczesna-Cordary D, Chandra M. Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca(2+) sensitivity and cross-bridge detachment kinetics. Am J Physiol Heart Circ Physiol. 2013 Jan 15;304(2):H253-9. doi: 10.1152/ajpheart.00572.2012. Epub 2012 Nov 9. (Medline PMID: 23144314)

Kazmierczak K, Yuan CC, Liang J, Huang W, Rojas AI, Szczesna-Cordary D. Remodeling of the heart in hypertrophy in animal models with myosin essential light chain mutations. Front Physiol. 2014 Sep 22;5:353. doi: 10.3389/fphys.2014.00353. (Medline PMID: 25295008)

Gomes AV, Kazmierczak K, Cheah JX, Gilda JE, Yuan CC, Zhou Z, Szczesna-Cordary D. Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains. J Muscle Res Cell Motil. 2015 Dec;36(6):447-61. doi: 10.1007/s10974-015-9434-0. Epub 2015 Dec 14. (Medline PMID: 26668058)

Wang Y, Ajtai K, Kazmierczak K, Szczesna-Cordary D, Burghardt TP. N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size. Biochemistry. 2016 Jan 12;55(1):186-98. doi: 10.1021/acs.biochem.5b00817. Epub 2015 Dec 29. (Medline PMID: 26671638)

Sitbon YH, Kazmierczak K, Liang J, Yadav S, Veerasammy M, Kanashiro-Takeuchi RM, Szczesna-Cordary D. Ablation of the N terminus of cardiac essential light chain promotes the super-relaxed state of myosin and counteracts hypercontractility in hypertrophic cardiomyopathy mutant mice. FEBS J. 2020 Sep;287(18):3989-4004. doi: 10.1111/febs.15243. Epub 2020 Feb 25. (Medline PMID: 32034976)

Sitbon YH, Diaz F, Kazmierczak K, Liang J, Wangpaichitr M, Szczesna-Cordary D. Cardiomyopathic mutations in essential light chain reveal mechanisms regulating the super relaxed state of myosin. J Gen Physiol. 2021 Jul 5;153(7):e202012801. doi: 10.1085/jgp.202012801. Epub 2021 May 20. (Medline PMID: 34014247)

Sitbon YH, Kazmierczak K, Liang J, Kloehn AJ, Vinod J, Kanashiro-Takeuchi R, Szczesna-Cordary D. Dual effect of N-terminal deletion of cardiac myosin essential light chain in mitigating cardiomyopathy. iScience. 2024 Jul 26;27(8):110591. doi: 10.1016/j.isci.2024.110591. (Medline PMID: 39211545)

Strain Development
The cDNA clones expressing the wild-type human ventricular essential light chain (huELCv) and the 43-amino-acid N-terminal ELC deletion mutant (huELCv-Δ43) were cloned into the unique SalI site of the plasmid, α-myosin heavy-chain clone 26. The resulting constructs contained about 5.5 kb of the mouse α-myosin heavy-chain promoter, including the first two exons and part of the third, followed by the WT/Δ43 cDNAs and a 600-bp 3′ untranslated region from the human growth hormone transcript. Founder mice were bred with B6SJL mice. The transgenic constructs were injected into ES cells, and founders were identified and tested for the presence of the transgene. All founder lines were bred to non-transgenic B6SJL mice, and multiple backcrosses to B6SJL/F1 mice were performed prior to using the animals in experiments. To maintain the original background, this line is bred to non-transgenic B6SJL/F1 mice twice a year (N=30).


Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain’s tissue samples taken when archived by or ordered from the assigned MMRRC Center.

Colony and Husbandry Information

Maintained under virus-free husbandry conditions.

For more information about this colony's health status contact csmmrrc@jax.org
Coat Color
Coat color varies.
Eye
Eye color varies.
MMRRC Breeding System
Backcross
Generation
This strain was established over 15 years ago, and to maintain continuity with the original background, we breed this line to non-transgenic B6SJL/F1 mice twice a year (N=30).
Overall Breeding Performance
Excellent
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined Undetermined
Homozygotes are fertile: Undetermined Undetermined
Hetero/Hemizygotes are fertile: Undetermined Undetermined
Age Reproductive Decline: 7 to 9 months 7 to 9 months
Average litter size
10 to 14
Recommended wean age
3 Weeks
Average Pups Weaned
10 to 14

Order Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Alexandra Vargas.

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.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Alexandra Vargas

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
075951-JAX-HET-F
075951-JAX-HET-M
075951-JAX-WT-F
075951-JAX-WT-M
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
$151.00 / $151.00
Non-Profit / For-Profit
Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org 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.