Strain Name:
C57BL/6J-Tg(Myh6-Sgk1*K141M)1Anr/Mmjax
Stock Number:
067427-JAX
Citation ID:
RRID:MMRRC_067427-JAX
Other Names:

Sgk1-KD, C57BL/6J-Tg(Myh6-Sgk1*K127M)1Anr

Strain Information

Tg(Myh6-Sgk1*K141M)1Anr
Name: transgene insertion 1, Anthony Rosenzweig
Type: Allele
Species: Multi-species
Chromosome: unknown
Myh6
Name: myosin, heavy polypeptide 6, cardiac muscle, alpha
Type: Gene
Species: Rattus norvegicus (norway rat)
Chromosome: 15
Sgk1
Name: serum/glucocorticoid regulated kinase 1
Type: Gene
Species: Rattus norvegicus (norway rat)
Chromosome: 1
Genetic Alterations
SGK1-KD mice express a cardiac-specific Sgk1 (serum/glucocorticoid regulated kinase) gene modified to harbor a lysine to methionine substitution at residue 141, initially reported as 127, (K141M). The mutation disrupts the catalytic activity of the kinase, generating a kinase dead (KD) mutant. Following pressure overload induced by TAC (transverse aortic constriction), SGK1-KD mice develop a protective response from fibrosis and heart failure.

HGVS nomenclature:

  • Genbank RefSeq - mRNA: NM_001193568.1
  • Genbank RefSeq, protein: NP_001180497.1
  • Variant, nucleic acid level: c.422_423delinsTG
  • Variant, amino acid level, predicted: p.Lys141Met (K141M)
    Check this variant: LUMC Mutalyzer
  • Note: This variant is known in the literature as "K127M", which uses positional information referencing to the shorter splice variant #3 (NM_019232.3, see LUMC Mutalyzer). The description here adheres to the HGVS nomenclature rules, which stipulate positional referencing to the longest splice isoform (Variant 1, NM_001193568.1).
ES Cell Line
Not applicable
Phenotype
Sgk1 (serum/glucocorticoid regulated kinase) encodes a PI3K-dependent, serine-threonine kinase which is activated by cardiac insult (transverse aortic constriction, TAC) or heart failure. SGK1-DN mice express HA-tagged rat Sgk1 harboring a lysine to methionine substitution at residue 141, initially reported as 127, (K141M) under the cardiomyocyte-specific Myh6 promoter. The mutation results in inhibition of catalytic activity of the kinase, generating a kinase dead (KD) mutant. Hemizygous SGK1-DN mice are viable and fertile. Mice exhibit no phenotype under normal conditions. Following TAC-induced stress, SGK1-DN mice maintain an adaptive protective response characterized by compensatory hypertrophy, absence of fibrosis and preserved contractility.

Mice carrying the constitutively active (CA) mutation in Sgk1 are available as MMRRC No. 067426.

MeSH Terms
  • Acetanilides/therapeutic use
  • Animals
  • Cardiomegaly, Exercise-Induced
  • Cardiomyopathy, Dilated/enzymology
  • Consensus Sequence
  • Disease Models, Animal
  • Electrocardiography
  • Enzyme Induction
  • Heart Failure/enzymology
  • Humans
  • Hypertension/complications
  • Immediate-Early Proteins/chemistry
  • Immediate-Early Proteins/deficiency
  • Immediate-Early Proteins/genetics
  • Immediate-Early Proteins/metabolism
  • Immediate-Early Proteins/physiology
  • Ion Channel Gating/drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NAV1.5 Voltage-Gated Sodium Channel/chemistry
  • NAV1.5 Voltage-Gated Sodium Channel/drug effects
  • NAV1.5 Voltage-Gated Sodium Channel/physiology
  • Phosphatidylinositol 3-Kinases/physiology
  • Phosphorylation
  • Piperazines/therapeutic use
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases/chemistry
  • Protein-Serine-Threonine Kinases/deficiency
  • Protein-Serine-Threonine Kinases/genetics
  • Protein-Serine-Threonine Kinases/metabolism
  • Protein-Serine-Threonine Kinases/physiology
  • Ranolazine
  • Sodium Channel Blockers/pharmacology
  • Sodium Channel Blockers/therapeutic use
  • Tachycardia, Ventricular/enzymology
  • Tachycardia, Ventricular/etiology
  • Ventricular Remodeling/physiology
Strain Development

The SGK1-KD transgenic construct contains a hemagluttinin (HA) tagged mutant rat Sgk1 (serum/glucocorticoid regulated kinase) sequence under the control of the cardiac-specific Myh6 (α-myosin heavy chain) promoter. The KD mutation replaces a lysine at residue 141, initially reported as 127, for a methionine (K141M), inactivating the kinase (kinase dead - KD). The linearized construct was microinjected into fertilized C57BL/6 oocytes. The strain has been maintained on C57BL/6J. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Suggested Control Mice
C57BL/6J
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 csmmrrc@jax.org. Older strains may not have this information.
  • Apoptosis
  • Cardiovascular
Donor
Anthony Rosenzweig, M.D., Massachusetts General Hospital.
Primary Reference

Das S, Aiba T, Rosenberg M, Hessler K, Xiao C, Quintero PA, Ottaviano FG, Knight AC, Graham EL, Boström P, Morissette MR, del Monte F, Begley MJ, Cantley LC, Ellinor PT, Tomaselli GF, Rosenzweig A. Pathological role of serum- and glucocorticoid-regulated kinase 1 in adverse ventricular remodeling. Circulation. 2012 Oct 30;126(18):2208-19. doi: 10.1161/CIRCULATIONAHA.112.115592. Epub 2012 Sep 26. (Medline PMID: 23019294)

Additional References

Park J, Leong ML, Buse P, Maiyar AC, Firestone GL, Hemmings BA. Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 1999 Jun 1;18(11):3024-33. doi: 10.1093/emboj/18.11.3024. (Medline PMID: 10357815)

Colony and Husbandry Information

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-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 csmmrrc@jax.org.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Other or uncertain
Generation
N/A
Overall Breeding Performance
Good
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: N/A N/A
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
4 to 6
Recommended wean age
3 weeks
Average Pups Weaned
4 to 6

Order Request Information

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 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 Catherine Lenich.

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.

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
067427-JAX-SPERM Cryo-preserved spermatozoa $437.00 / $437.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
067427-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / $2,022.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
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.