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Strain Name:
C57BL/6-Erbb4em1Corf/Mmmh
Stock Number:
075961-MU
Citation ID:
RRID:MMRRC_075961-MU
Other Names:
TACE-uncleavable ErbB4-JMa

Strain Information

QUALITY CONTROL OF C57BL/6-Erbb4em1Corf/Mmmh  |  University of Missouri
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3YES
Genetic backgroundYES
Viability of genotypes available for distributionYES
Specific Pathogen- Status YES
Recoverability of cryopreserved sperm/embryos4 YES
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 distributionYES
Fecundity/breeding performance YES

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.

Erbb4em1Corf
Name: erb-b2 receptor tyrosine kinase 4; endonuclease-mediated mutation 1, Gabriel Corfas
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 1
Alteration at locus: CRISPR
Erbb4
Name: erb-b2 receptor tyrosine kinase 4
Synonyms: ErbB4, Her4
Type: Gene
Species: Mouse
Chromosome: 1
NCBI: 13869
HGNC: HGNC:3432
Homologene: 21084
Genetic Alterations
CRISPR-targeting of exon 16 introduced point mutations responsible for the amino acid substitutions of histidine with asparagine at position 641 (H641N) and serine with proline at position 642 (S642P). These mutations block TACE cleavage.
ES Cell Line
Not applicable
Phenotype
Although engineered to block ErbB4-JMa cleavage and subsequent nuclear signaling, the E4ICD fragment remained detectable in tissue lysates from “TACE-uncleavable ErbB4-JMa” (ErbB4TUC/TUC) mice, indicating that the H641N;S642P substitutions in Erbb4 exon 16a did not prevent ErbB4-JMa cleavage in vivo. In contrast, E4ICD formation was completely abolished in heterologous cells.
MeSH Terms
  • Animals
  • Mice
  • Mice, Knockout
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Receptor, ErbB-4/genetics
  • Receptor, ErbB-4/metabolism
  • Signal Transduction
  • Tyrosine/metabolism
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.
Donor
Gabriel Corfas, Ph.D., University of Michigan.
Primary Reference

Doherty R, MacLeod BL, Nelson MM, Ibrahim MMH, Borges BC, Jaradat NW, Finneran MC, Giger RJ, Corfas G. Identification of in vivo roles of ErbB4-JMa and its direct nuclear signaling using a novel isoform-specific knock out mouse. Sci Rep. 2022 Oct 14;12(1):17267. doi: 10.1038/s41598-022-21598-2. Erratum in: Sci Rep. 2022 Dec 1;12(1):20748. doi: 10.1038/s41598-022-25021-8. (Medline PMID: 36241655)

Strain Development
Single guide RNAs (sgRNA) were designed to create cut sites in the Erbb4-JMa sequence within exon 16. These guides were expected to create a double strand break and introduce the ultramer oligonucleotide bearing the H641N;S642P mutations by homology directed repair, replacing the wild type sequence with the mutant sequence in exon 16. The sgRNAs were co-injected into fertilized C57BL/6 eggs with the CRISPR/Cas9 components and the ultramer oligonucleotide bearing the mutations. Sequence analysis of Erbb4 exon 16 identified 3 mice with the correct mutations (H641N;S642P). All founders with discernable H641N;S642P mutations were crossed with wild type mice to create obligatory heterozygotes and Erbb4 exon 16 sequence of the progeny was analyzed. Of the founders, only one mouse had the H641N;S642P mutation. Male and female heterozygote offspring from the founders were inbred to create homozygotes and back-crossed onto the C57BL/6 background.


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

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
Breeding Scheme(s)
Backcrossed to C57BL/6J or inbred.
Generation
N/A
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 4 to 6 months 4 to 6 months
Bred to Homozygosity
Yes
Average litter size
Variable
Recommended wean age
3 Weeks
Average Pups Weaned
Variable

Order 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.

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

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 Emily Bowers

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
075961-MU-SPERM Cryo-preserved spermatozoa $437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
075961-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.