Strain Detail Sheet

Strain Name    :

129S6/SvEv(B6)-Map3k4tm1Glj/Mmnc

Stock Number :

032019-UNC

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Target: Map3k4tm1Glj
Name: targeted mutation 1, Gary L Johnson
Alteration at locus: Knock-In
Target: Map3k4
Name: mitogen-activated protein kinase kinase kinase 4
Chromosome: 17
Alteration at locus: Knock-In

Genetic Alterations:
Two mutations were generated in exon 21. A silent mutation introduced a SacI site in codon 1357, from CTG to CTC. In codon 1361, a single nucleotide change from AAG to AGG introduced a substitution of lysine for agrginine. The neomycin gene was introduced into intron 21 in the reverse direction.

Genotype Determination:

ES Cell Line: TC1/TC-1 derived from 129S6/SvEvTac

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

Phenotype

Homozygous: Embryonic and perinatal lethality due to neural tube, skeletal, and placental defects.

Heterozygous: Similar defects as homozygotes but with reduced penetrance.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Map3k4tm1Glj/Map3k4+
        involves: 129S6/SvEvTac * C57BL/6
  • nervous system phenotype
    • abnormal neural tube morphology/development (MGI Ref ID J:101350)
      • about 25% of heterozygous embryos display neural tube defects
  • skeleton phenotype
    • abnormal sternum morphology (MGI Ref ID J:101350)
      • in heterozygotes with asymmetric attachment of the ribs severe curvature of the sternum is seen
      • asymmetric rib-sternum attachment (MGI Ref ID J:101350)
        • asymmetric attachment of the ribs to the sternum is seen in 5 - 8% of heterozygotes
    • abnormal vertebrae morphology (MGI Ref ID J:101350)
    • decreased rib number (MGI Ref ID J:101350)
      • in heterozygotes with asymmetric attachment of the ribs some ribs are absent
  • embryogenesis phenotype
    • abnormal neural tube morphology/development (MGI Ref ID J:101350)
      • about 25% of heterozygous embryos display neural tube defects
Map3k4tm1Glj/Map3k4tm1Glj
        involves: 129S6/SvEvTac * C57BL/6
  • mortality/aging
    • partial perinatal lethality (MGI Ref ID J:101350)
      • about 2/3 of homozygous pups die at birth
  • nervous system phenotype
    • abnormal neural tube morphology/development (MGI Ref ID J:101350)
      • about 50% of homozygous embryos display neural tube defects
      • craniorachischisis (MGI Ref ID J:101350)
        • in pups that die at birth craniorrhachischisis is occasionally seen
      • spina bifida (MGI Ref ID J:101350)
        • about 7% of surviving homozygotes display sacral spina bifida with a curl proximal to the tail root and an open spinal cord and vertebral canal covered by skin shortly after birth
        • pups that die immediately after birth have severe open spine defects and at E18.5 about 20% of homozygotes display spina bifida
    • exencephaly (MGI Ref ID J:101350)
      • at E14.5 exencephaly is seen and increased apoptosis is seen at E9.5 in the hindbrain of all exencephalic embryos
  • skeleton phenotype
    • abnormal vertebrae morphology (MGI Ref ID J:101350)
      • vertebral malformations including in some severely affected pups rachischisis and craniorrhachischisis
      • abnormal caudal vertebrae morphology (MGI Ref ID J:101350)
        • bone remodeling is seen in the tail; however chondrogenesis is normal
    • asymmetric rib-sternum attachment (MGI Ref ID J:101350)
      • asymmetric attachment of the ribs to the sternum is seen in 75% of homozygotes
    • scoliosis (MGI Ref ID J:101350)
  • embryogenesis phenotype
    • abnormal neural tube morphology/development (MGI Ref ID J:101350)
      • about 50% of homozygous embryos display neural tube defects
      • craniorachischisis (MGI Ref ID J:101350)
        • in pups that die at birth craniorrhachischisis is occasionally seen
      • spina bifida (MGI Ref ID J:101350)
        • about 7% of surviving homozygotes display sacral spina bifida with a curl proximal to the tail root and an open spinal cord and vertebral canal covered by skin shortly after birth
        • pups that die immediately after birth have severe open spine defects and at E18.5 about 20% of homozygotes display spina bifida
  • reproductive system phenotype
    • asthenozoospermia (MGI Ref ID J:101350)
    • male infertility (MGI Ref ID J:101350)
      • surviving males are infertile
    • oligozoospermia (MGI Ref ID J:101350)
  • limbs/digits/tail phenotype
    • abnormal caudal vertebrae morphology (MGI Ref ID J:101350)
      • bone remodeling is seen in the tail; however chondrogenesis is normal
  • growth/size phenotype
    • omphalocele (MGI Ref ID J:101350)
      • in some pups that die at birth and in some embryos at E14.5 omphalocele is occasionally seen

Strain of Origin: 129S6/SvEvTac

Strain genetic background: 129S6/SvEvTac

Strain Development: Original mutant mouse was backcrossed seven times with 129 SVEV. Mice are maintained by heterozygote intercrosses due to lethalitiy of homozygote mutant.

Strain Genetic Background Validation: A sample from this MMRRC strain was analyzed using the Mouse Universal Genotyping Array (MUGA) and MMRRC computational tools were used to assess the genetic background. A summary of the data can be found here.

MMRRC StrainReference StrainsGenomic makeup (Mb)
Strain Name MMRRC ID # Reference 1 Reference 2 Ref 1 Ref 2 Het Unknown
129S6/SvEv(B6)-Map3k4tm1Glj/Mmnc MMRRC:032019-UNC 129S6 C57BL/6J 2521 26 35 0


Suggested Control Mice:

Wild-type littermates or 129S6/SvEvTac mice

Research Applications

  • Apoptosis
  • Cell Biology
  • Developmental Biology
  • Immunology and Inflammation
  • Models for Human Disease
  • Reproduction

Strain Origin

Donor: Gary L Johnson, Ph.D., University of North Carolina at Chapel Hill School of Medicine.

Primary Reference:

  • Abell AN; Rivera-Perez JA; Cuevas BD; Uhlik MT; Sather S; Johnson NL; Minton SK; Lauder JM; Winter-Vann AM; Nakamura K; Magnuson T; Vaillancourt RR; Heasley LE; Johnson GL, Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryo., Mol Cell Biol 2005 Oct;25(20):8948-59 (Medline PMID: 16199873)
  • Abell, A.N., Granger, D.A., Johnson, N.L., Vincent-Jordan, N., Dibble, C.F.and Johnson, G.L. Trophoblast stem cell maintenance by fibroblast growth factor 4 requires MEKK4 activation of Jun N-terminal kinase. Mol Cell Biol 2009 29: 2748-2761 (Medline PMID: 19289495)

Colony and Husbandry Information

Special Considerations

The mice have an increased frequency of eye infections; this can be treated with antibiotic ointment.

Health Status Report

For more information about this colony's health status contact mmrrc_health@med.unc.edu

Appearance

Coat color: Brown

Other:

Curly/kinky tail in surviving homozygotes. Increased frequency of eye infections. Small litter size.

Breeding

MMRRC Breeding System: Sib-mating

Breeding Scheme(s):

  • Heterozygous female x Heterozyguos male littermate.
  • Due to placental and developmental defects, a larger breeding colony needed to maintain the colony.

Generation: N7

Overall Breeding Performance: Poor: Due to shortened reproductive lifespan, future breeding pairs should be saved from the first litter should a second litter is not produced.

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: No No
Homozygotes are fertile:
Heterozygotes are fertile: Reduced Reduced

Age Reproductive Decline: 5 months 5 months

Average litter size: 2-3

Recommended wean age: 3 weeks

Order Request Information

Availability Level

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at mmrrc@med.unc.edu for more details.

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.

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

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
032019-UNC-HET-FHeterozygous female
032019-UNC-HET-MHeterozygous male
032019-UNC-WT-FWild type female
032019-UNC-WT-MWild type male
$218.00
Non-Profit
Per Mouse The mmrrc@med.unc.edu may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
032019-UNC-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2

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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