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Strain Name:
129S.B6-Kcnj5tm1Clph/Mmucd
Stock Number:
075865-UCD
Citation ID:
RRID:MMRRC_075865-UCD
Other Names:
GIRK4 knockout

Strain Information

QUALITY CONTROL OF 129S.B6-Kcnj5tm1Clph/Mmucd  |  University of California at Davis
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 sequence3 n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distribution n.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.

Kcnj5tm1Clph
Name: potassium inwardly-rectifying channel, subfamily J, member 5; targeted mutation 1, David E Clapham
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 9
Alteration at locus: Knockout
Kcnj5
Name: potassium inwardly-rectifying channel, subfamily J, member 5
Synonyms: Kir3.4, GIRK4
Type: Gene
Species: Mouse
Chromosome: 9
Alteration at locus: Knockout
NCBI: 16521
VEGA: 9
HGNC: HGNC:6266
Homologene: 20248
Genetic Alterations
A neomycin selection cassette replaced exon 1, which encodes the amino and carboxyl termini, both transmembrane domains, and the putative pore-lining sequence. Northern blot analysis of total atrial RNA showed an absence of normal transcript in homozygous mutant mice. mRNA levels of other K+ inwardly-rectifying channels, were shown to be unaffected by the targeting event by rehybridization of the Northern blot using Kcnj3-, Kcnj6- and Kcnj9-specific probes. Western blot analysis of protein extracts derived from atrial cell membranes showed that the targeted Kcnj5 protein product was absent, and levels of both glycosylated and unglycosylated forms of Kcnj3 were significantly reduced in homozygous mutant mice.
ES Cell Line
ES Cells derived from 129X1/SvJ
Phenotype

Acetylcholine (ACh), released from the stimulated vagus nerve, decreases heart rate via modulation of several types of ion channels expressed in cardiac pacemaker cells. One of the ion channels, the muscarinic-gated potassium channel, IKACh has been implicated in vagally-mediated heart rate regulation.

The Kcnj5tm1Clph (GIRK4 knockout) line was established to assess the role of IKACh in in vivo heart regulation.

  • Heterozygous Kcnj5tm1Clph mice are indistinguishable from wildtype mice.
  • Homozygous Kcnj5tm1Clph mice have altered cardiac ACh activated potassium conductance, showing no IKACh activity observed in isolated atrial myocyte patches from knockout mice. In contrast to wild-type mice, the heart rate variability (HRV) spectra of GIRK4-deficient mice had minimal power in the low frequency range and significanlty lower spectral power in the high frequency range. While the very low frequency component of the HRV did not vary between genotypes. Knockout mice had significantly reduced GIRK1 protein levels in the atria.

Resting heart rate in unrestrained conscious wild-type and Kcnj5tm1Clph knockout mice were virtually identical, indicating that other signaling pathways involved in heart rate regulation can balance the missing IKACh current.

MeSH Terms
  • Adenosine/pharmacology
  • Animals
  • Electrocardiography
  • Electrophysiology
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Heart Rate/drug effects
  • Heart Rate/physiology
  • Ion Channel Gating/physiology
  • Mice
  • Mice, Inbred C57BL/genetics
  • Mice, Knockout/genetics
  • Mice, Knockout/physiology
  • Muscarine/metabolism
  • Patch-Clamp Techniques
  • Potassium Channels/genetics
  • Potassium Channels/physiology
  • Potassium Channels, Inwardly Rectifying
  • Stimulation, Chemical
  • Telemetry
  • Vagus Nerve/physiology
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
  • Neurobiology
Donor
David Clapham, M.D., Ph.D., Boston Children's Hospital - HHMI.
Kevin Wickman, Ph.D., University of Minnesota.
Primary Reference

Wickman K, Nemec J, Gendler SJ, Clapham DE. Abnormal heart rate regulation in GIRK4 knockout mice. Neuron. 1998 Jan;20(1):103-14. doi: 10.1016/s0896-6273(00)80438-9. (Medline PMID: 9459446)

Strain Development
A ∼2.7 kb fragment containing coding sequence exon 1 was replaced with a targeting vector: neomycin under the control of the mouse PGK promoter (NEO-PGK). The diptheria toxin gene (DTA), driven by the thymidine kinase promoter, was included in the targeting vector to enrich for homologous recombinants. 129Sv/J ES cells were transfected with the linearized GIRK4 targeting vector, and 480 colonies surviving G418 selection were picked and screened by PCR and Southern blotting for homologous recombinants.

Two, properly targeted ES cell clones, were injected into 2.5 day old C57Bl6/J blastocysts. Blastocysts were implanted into CD1 female mice to produce chimera. Chimeric mice were identified on the basis of agouti/chinchilla pigmentation in the coat. Male chimeric mice were crossed with both C57BL6/J (at least 10 backcrosses) and 129Sv/J females to screen for germline transmission of the targeted GIRK4 allele and to maintain the targeted mutation on inbred (129Sv) and outbred (C57BL6/129Sv) genetic backgrounds. All mice were genotyped by Southern blotting or by PCR screening using tail DNA.


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@ucdavis.edu.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Random intra-strain mating
Generation
28
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: Undetermined Undetermined
Average litter size
4 to 6
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

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@ucdavis.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 Naomi Walsh.

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 Donor is required for for-profit entities to use this strain. For more information, please contact Naomi Walsh

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
075865-UCD-SPERM Cryo-preserved spermatozoa $546.25 / $882.81
Non-Profit / For-Profit
Aliquot Approximate quantity3
075865-UCD-RESUS Litter recovered from cryo-archive $5,892.91 / $6,181.91
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.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.