Strain Detail Sheet

Strain Name    :

B6.129S1-Kcnj10tm1Lst/Mmnc

Stock Number :

000209-UNC

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Kcnj10tm1Lst
Name: targeted mutation 1, Henry A Lester
Chromosome: 1: 93.5 cM
Alteration at locus: Targeted Mutation
Gene Symbol: Kcnj10
Name: potassium inwardly-rectifying channel, subfamily J, member 10
Chromosome: 1
Alteration at locus: Targeted Mutation

Genetic Alterations:
A neomycin resistance gene replaces amino acids 33­266 in the Kir4.1 deduced primary sequence and thus contains the putative transmembrane domains and part of the C terminus of the Kir4.1 polypeptide.

Genotype Determination:

ES Cell Line: CJ7

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous: Key points from published papers. Kir4.1 knockout mice die at P11-18. Mice display marked motor impairment, and the cellular basis is hypomyelination in the spinal cord, accompanied by severe spongiform vacuolation, axonal swellings, and degeneration. Dysmyelination is extensive in many parts of the brain. The brain stem is most affected and during the first 2 weeks of life, the changes extend forward to the frontal parts like corpus callosum. The slow PIII response of the light-evoked electroretinograms (ERG), which is generated by K1 fluxes through Muller cells, is totally absent in retinas from Kir4.1 knockout mice. Mice lacking the KCNJ10 (Kir4.1) K+ channel in strial intermediate cells did not generate an endocochlear potential. Endolymph volume and K+ concentration were reduced. Startle response experiments suggest that Kir4.1 knockout mice are profoundly deaf, whereas Kir4.1+/- mice react like wild type mice to acoustic stimuli. In Kir4.1 knockout mice, the Reissners membrane is collapsed, the tectorial membrane is swollen, and spiral ganglion neuron central processes degenerate. In the vestibular ganglia,neuronal cell death with apoptotic features is observed.

Heterozygous: show little phenotype.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Kcnj10tm1Lst/Kcnj10+
        involves: 129S1/Sv * C57BL/6J
  • vision/eye phenotype
    • abnormal eye physiology (MGI Ref ID J:63635)
      • in situ whole-cell patch-clamp recordings of the input resistance of Muller cells showed that the input resistance of heterozygous mutant cells is almost precisely double that of wild-type Muller cells, indicating a gene dosage effect
      • only one-half as many channels were expressed in Muller cells in which one of the two channel genes was inactivated
Kcnj10tm1Lst/Kcnj10tm1Lst
        involves: 129S1/Sv * C57BL/6J
  • mortality/aging
    • complete postnatal lethality (MGI Ref ID J:108878)
      • most deaths occur at P9-P21
    • complete postnatal lethality (MGI Ref IDs J:77663, J:63635)
      • after P7, homozygotes show a higher rate of mortality; however, most mutants survive up to 3 weeks of age, permitting examination of retinal physiology after eyelid opening (P13 and P14) (MGI Ref ID J:63635)
      • the first deaths occur at P8, with 100% mortality at P24 (MGI Ref ID J:77663)
  • behavior/neurological phenotype
    • abnormal motor capabilities/coordination/movement (MGI Ref ID J:77663)
      • by P10-P12, homozygotes exhibit defects in controlling voluntary movements, posture, and balance; these defects increase in severity over time
      • abnormal motor coordination/ balance (MGI Ref IDs J:77663, J:63635)
        • homozygotes exhibit motor coordination deficits, first apparent at ~2 weeks of age (MGI Ref ID J:63635)
        • in contrast to wild-type littermates, homozygotes are unable to climb a grid at an 80

          Strain of Origin: mixed 129SV and C57BL/6 mixed 129SV and C57BL/6 (> 6 generations)

          Strain genetic background: mixed 129SV and C57BL/6 (> 6 generations)

          Suggested Control Mice:

          • Wildtype littermates

Research Applications

  • Apoptosis
  • Developmental Biology
  • Models for Human Disease
  • Neurobiology
  • Research Tools
  • Sensorineural

Strain Origin

Donor: Henry Lester, Ph.D., California Institute of Technology

Primary Reference:

Kofuji P, Ceelen P, Zahs KR, Surbeck LW, Lester HA, Newman EA. Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: phenotypic impact in retina. J Neurosci. 2000 Aug 1;20(15):5733-40. (Medline PMID: 10908613)

Colony and Husbandry Information

Special Considerations

None

Health Status Report

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_health@med.unc.edu.

Appearance

Coat color: Black

Other:

Breeding

MMRRC Breeding System: Back-cross

Breeding Scheme(s):

  • Heterozygous female x C57BL/6 male
    Heterozygous male x C57BL/6 female 

Generation: Unknown

Overall Breeding Performance: Normal

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: No No Knockout mice die at P11-18. Mice display marked motor impairment.
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes

Age Reproductive Decline: Unknown Unknown

Average litter size: 6 - 8

Recommended wean age: 3 weeks

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

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.

Fees

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 $)
Units Notes
000209-UNC-RESUSLitter recovered from cryo-archive
$2,022.00 / $4,109.00
Non-Profit / For-Profit
Litter Recovered litter1; additional fees for any special requests.

1 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.

2 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.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

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 above). 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.



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.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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Generated: 04/24/2014