Strain Name:
B6J.129S6-Tph2tm1Mca/McaMmnc
Stock Number:
043618-UNC
Citation ID:
RRID:MMRRC_043618-UNC
Other Names:
Tph2 R439H KI

Strain Information

Tph2tm1Mca
Name: tryptophan hydroxylase 2; targeted mutation 1, Marc G Caron
Synonyms: R439H Tph2, Tph2-KI
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 10
Alteration at locus: Knock-In
Tph2
Name: tryptophan hydroxylase 2
Type: Gene
Species: Mouse
Chromosome: 10
Alteration at locus: Knock-In
NCBI: 216343
Homologene: 27831
Genetic Alterations

Exon 10 and 11 were replaced with a floxed neo cassette and another copy of exon 10 and 11 with a nucleotide transition of G to A at position 1449 within exon 11. This transition predicts a histidine-to-arginine amino acid substitution at position 439 (R439H). The neo cassette was removed by transient cre-mediated recombination in ES cells. This allele was created to mimic the R441H mutation identified in humans that leads to 80% reduced enzymatic activity in PC12 cells.

HVGS Nomenclature
  • Genbank RefSeq - mRNA: NM_173391.3
  • Genbank RefSeq, protein: NP_775567.2
  • Variant, nucleic acid level: c.1316G>A
  • Variant, amino acid level, predicted: p.Arg439His
  • Check this variant: LUMC Mutalyzer
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    CMTI-1 derived from 129S6/SvEvTac
    Phenotype

    Homozygous: ~80% less brain serotonin

    Heterozygous: ~50% less brain serotonin

    Mammalian Phenotype Terms
    Allelic Composition: (Genetic Background: )

    MeSH Terms
    • Amino Acid Substitution/genetics
    • Animals
    • Behavior, Animal/physiology
    • Cell Line
    • Glycogen Synthase Kinase 3/antagonists & inhibitors
    • Glycogen Synthase Kinase 3/physiology
    • Glycogen Synthase Kinase 3 beta
    • Humans
    • Immobilization/physiology
    • Interpersonal Relations
    • Locomotion/genetics
    • Locomotion/physiology
    • Mice
    • Mice, Inbred C3H
    • Mice, Inbred C57BL
    • Mice, Mutant Strains
    • Mutagenesis, Site-Directed
    • Serotonin/biosynthesis
    • Serotonin/deficiency
    • Serotonin/physiology
    • Signal Transduction/genetics
    • Tryptophan Hydroxylase/genetics
    • Tryptophan Hydroxylase/physiology
    Strain Development
    Developed with CMTI-1 embryonic stem cells derived from 129S6/SvEvTac. The chimeras were bred to C57BL/6J, then inbred for 30+ generations, then backcrossed to C57BL/6J for >10 generations.
    Suggested Control Mice
    Wild-type littermates
    MMRRC Genetic QC Summary
    Genetic QC analysis (GQC) was performed on representative samples from the donor submission and provides a baseline reference. Regardless of the material ordered (live mice, sperm, embryos, resuscitated animals), the provided material is guaranteed to contain the primary genetic alteration of interest; however, the composition of the genetic background may vary (See Reproducibility sections of the report for details). The impact of genetic background on previously reported phenotypes has not been evaluated.

    GQC analysis was done on two samples LX0733 (XX), HX0878 (XY) at the time of importation and the conclusions are consistent in all samples. The results of the analysis are congruent with the SDS and HX0878 is the representative sample selected for the report. The primary (host) background is C57BL/6J. The secondary (donor) background is consistent with 129S6/SvEvTac, which is indicated in the submission and the SDS as the donor strain. The mitochondrial genome is consistent with at least one backcross to a female from the host background. The Y chromosome is consistent with at least one backcross to a male from the host background. The region containing the allele of interest has the expected donor background (129S6/SvEvTac). Both samples are heterozygous for the donor background at the locus. None of the constructs detectable by MiniMUGA are present.

    The genome of MMRRC:043618 mice is 99.3 % inbred and 100% congenic at the strain level. 0.7% of the genome is segregating for the secondary (donor) background. The level of congenicity estimated by miniMUGA is consistent with the number of backcross generations reported in the SDS.
    MiniMUGA Sample Report
    • Neurobiology
    • Research Tools
    Donor
    Marc Caron, Ph.D., Duke University.
    Primary Reference

    Beaulieu JM, Zhang X, Rodriguiz RM, Sotnikova TD, Cools MJ, Wetsel WC, Gainetdinov RR, Caron MG. Role of GSK3 beta in behavioral abnormalities induced by serotonin deficiency. Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1333-8. doi: 10.1073/pnas.0711496105. Epub 2008 Jan 22. (Medline PMID: 18212115)

    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
    Eye
    Black
    MMRRC Breeding System
    Sib-mating and 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 HO and WT pups are desired, HO x HO and WT x WT matings are set up.
    Generation
    N10 (C57BL/6J), F30+
    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: 8 to 12 months 8 to 12 months
    Average litter size
    5-9
    Recommended wean age
    3 weeks
    Average Pups Weaned
    5-9

    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@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
    043618-UNC-RESUS Litter recovered from cryo-archive $2,914.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.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.