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Strain Name:
C57BL/6J-Ank2em1Melr/Mmmh
Stock Number:
071828-MU
Citation ID:
RRID:MMRRC_071828-MU
Other Names:
AnkB p.E1371G

Strain Information

Ank2em1Melr
Name: ankyrin 2, brain; endonuclease-mediated mutation 1, Mona El Refaey
Synonyms: AnkBp.E1458G+, E1458G+
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 3
Alteration at locus: CRISPR
Ank2
Name: ankyrin 2, brain
Synonyms: ankyrin B, Ank-2, Ankyrin-2, Ankyrin-B, Gm4392
Type: Gene
Species: Mouse
Chromosome: 3
Alteration at locus: CRISPR
NCBI: 109676
HGNC: HGNC:493
Genetic Alterations
CRISPR/Cas9 technology generated a GAA to GGC change resulting in a glutamic acid to glycine substitution at amino acid 1371 (p.E1371G) in the spectrin-binding domain. Multiple silent coding changes were also introduced to block the Cas9 targets. This corresponds to the human p.E1458G variant associated with arrhythmias and structural remodeling.
Phenotype
At baseline, young AnkBp.E1371G+/+ mice lacked significant structural or electrical abnormalities. However, aged AnkBp.E1371G+/+ mice displayed both electrical and structural phenotypes at baseline including bradycardia and aberrant heart rate variability, structural remodeling, and fibrosis. Young and old AnkBp.E1371G+/+ mice displayed ventricular arrhythmias following acute (adrenergic) stress. In addition, young AnkBp.E1371G+/+ mice displayed structural remodeling following chronic (transverse aortic constriction) stress.

Conditional phenotype: No

MeSH Terms
  • Animals
  • Humans
  • Mice
  • Adrenergic Agents/metabolism
  • Ankyrins/metabolism
  • Disease Models, Animal
  • Ion Channels/metabolism
  • Mice, Knockout
  • Myocytes, Cardiac/metabolism
  • Phenotype
  • Aging/metabolism
Strain Development
A knock-in mouse to mimic the human variant at amino acid 1458 of human ANK2 was generated by The University of Michigan Transgenic Animal Model Core. A single guide RNA was designed to create a CRISPR-induced indel in a region close to codon 1371 in mouse (which corresponds to 1458 in the human sequence). The guide RNA along with Cas9 were microinjected into (C57BL/6J x SJL/J)F1 zygotes. Chimera mice were screened for the single amino acid substitution at the guide sequence. Germline mice were generated by breeding chimeras to C57BL/6J mice. After germline transmission, mice were genotyped and sequenced to confirm the GAA to GGC substitution. Mice were backcrossed on a C57BL/6 background for five generations. The whole colony was produced from a single founder.
Suggested Control Mice
Littermate controls
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 mmrrc@missouri.edu. Older strains may not have this information.
  • Cardiovascular
  • Models for Human Disease
Donor
Mona El Refaey, Ph.D., Ohio State University.
Peter Mohler, Ph.D., The Ohio State University.
Primary Reference

Wallace MJ, Malhotra N, Mariángelo JIE, Stevens TL, Young LJ, Antwi-Boasiako S, Abdallah D, Takenaka SS, Cavus O, Murphy NP, Han M, Xu X, Mangoni ME, Hund TJ, Roberts JD, Györke S, Mohler PJ, El Refaey M. Impact of stress on cardiac phenotypes in mice harboring an ankyrin-B disease variant. J Biol Chem. 2023 Jun;299(6):104818. doi: 10.1016/j.jbc.2023.104818. Epub 2023 May 12. (Medline PMID: 37182735)

Colony and Husbandry Information

Colony Surveillance Program and Current Health 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 mmrrc@missouri.edu.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Random intra-strain mating
Generation
5
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 10 to 12 months Greater than 12 months
Bred to Homozygosity
Yes
Average litter size
7 to 9
Recommended wean age
3 Weeks
Average Pups Weaned
7 to 9

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 mmrrc@missouri.edu for more information.

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
071828-MU-SPERM Cryo-preserved spermatozoa $437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
071828-MU-RESUS Litter recovered from cryo-archive $2,624.00 / $5,340.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu 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.