Strain Name:
B6J.129X1-Slc6a2tm1Mca/Mmnc
Stock Number:
043613-UNC
Citation ID:
RRID:MMRRC_043613-UNC
Other Names:
Norepinepherine Transporter KO, NET KO

Strain Information

Slc6a2tm1Mca
Name: solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2; targeted mutation 1, Marc G Caron
Synonyms: NET-, NET KO
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 8
Alteration at locus: Knockout
Slc6a2
Name: solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2
Synonyms: NET, Slc6a5, norepinephrine transporter, NE transporter
Type: Gene
Species: Mouse
Chromosome: 8
Alteration at locus: Knockout
NCBI: 20538
Homologene: 816
Genetic Alterations
Knockout of the norepinephrine transporter gene Slc62a.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    AK7 derived from 129S4/SvJaeSor
    Phenotype

    Homozygous: Homozygous NET-/- mice are viable and fertile and showed reduced body temperature (approx1°C) and body weight (approx20%) relative to wild-type controls. In the prefrontal cortex, hippocampus and cerebellum, tissue concentrations of NE were reduced by approximately 55−70% in the NET-/- mice.

    Hetero/Hemizygous: not reported

    The Norepinephrine transporter (NET) KO mice are phenotypically distinguishable from any other gene knockouts that altered the levels of norepinephrine in tissues. Specifically, inactivation of the NET selectively leads to increased levels of extracellular norepinephrine (NE) by inhibiting the reuptake or clearance of Norepinephrine from the extracellular space. Behaviorally, the NET KO mice are significantly less immobile in the swim test, display increased struggling behavior in the tail suspension test, and in the same tail suspension test their struggling behavior matches that of wild type mice treated with small molecule inhibitors of NET, serotonin or dopamine transporters (SERT and DAT). In the open field, NETKO mice are slightly less active and also habituate slightly faster to the novel environment. When challenged with the psychostimulants cocaine or amphetamine, NETKO mice show an exaggerated open field locomotor response. In a cocaine sensitization paradigm, NETKO mice are as active on the first exposure to cocaine as wild type mice are following a 5day exposure to cocaine.  In the Place-Preference paradigm NETKO show an exaggerated preference for the cocaine side compared to WT mice treated for six consecutive days.  Interestingly, ablation of the NET gene seems to influence striatal dopaminergic homeostasis by reducing the extracellular levels of dopamine and its degradation products but enhancing both the sensitivity and the behavioral responses to D2/D3 agonists. NETKO mice have also been used to probe fro gastrointestinal and cardiovascular phenotypes. Results of these studies can be found by a simple literature search.

    Mammalian Phenotype Terms
    Allelic Composition: (Genetic Background: )

    Strain Development
    Chimera was bred to C57Bl/6J from Jackson Labs then back crossed for >10 generations. After that, the colony was maintained by sib matings.
    Suggested Control Mice
    Wild-type littermates
    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@med.unc.edu. Older strains may not have this information.
    • Neurobiology
    • Research Tools
    Donor
    Marc Caron, Ph.D., Duke University.

    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_health@med.unc.edu.
    Coat Color
    black
    Other
    A lower percentage of offspring are HO compared to predicted Mendelian proportions. HO pups survive well with a later weaning age, and HO x HO matings do produce HO pups.
    MMRRC Breeding System
    Backcross
    Breeding Scheme(s)
    The colony is now maintained with het x het matings in order to produce homozygous pups and littermate wildtype controls. When a large number of hom pups are desired, hom x hom matings are set up.
    Generation
    >10
    Overall Breeding Performance
    Good
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Reduced Reduced
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 4 to 6 months 4 to 6 months
    Bred to Homozygosity
    No
    Average litter size
    5-9
    Recommended wean age
    3-4 weeks

    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@med.unc.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.

    The donor or their institution limits the distribution to non-profit institutions only.

    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
    043613-UNC-EMBRYO Cryo-preserved embryos $1,404.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
    043613-UNC-SPERM Cryo-preserved spermatozoa $564.00 / Non-Profit Aliquot Approximate quantity3
    043613-UNC-RESUS Litter recovered from cryo-archive $2,914.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.

    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.