Strain Name:

129S-Ywhaetm1Awb/J

Stock Number:

008715

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Mice carrying this targeted mutation of Ywhae (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide) exhibit hippocampal defects, neuronal migration abnormalities, and increased apoptosis in the brain. This mutant mouse strain may be useful in studies of Miller-Dieker Lissencephaly Syndrome and neuronal migration during brain development.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
 
Donating InvestigatorDr. Anthony Wynshaw-Boris,   Case Western Reserve University, School of Medicine

Description
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Most homozygotes die at birth, less than 1% of homozygotes survive to adulthood. Survivors remain smaller in size than wildtype controls. No gene product (protein) is detected by immunoblot analysis of brain tissue from homozygotes. Homozygotes exhibit hippocampal defects with thinning of the cortex, hippocampal pyramidal cell layer disorganization and neuronal migration abnormalities. Heterozygotes exhibit less severe hippocampal defects. Mutants have increased apoptosis in the brain. This mutant mouse strain may be useful in studies of Miller-Dieker Lissencephaly Syndrome and neuronal migration during brain development.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt parts of exons 2 and 3. The construct was electroporated into 129S6/SvEvTac derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to 129S6 mice. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least one generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
   002448 129S1/SvImJ
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Left Ventricular Noncompaction 1; LVNC1
Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.
Miller-Dieker Lissencephaly Syndrome; MDLS
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ywhaetm1Awb/Ywhae+

        involves: 129S6/SvEvTac
  • cardiovascular system phenotype
  • abnormal heart left ventricle morphology
    • thinner left ventricle   (MGI Ref ID J:192860)
  • thin ventricle myocardium compact layer   (MGI Ref ID J:192860)
  • ventricular septal defect
    • 20% of mutants exhibit ventricular septal defects at E14.5, but only 7% of mutants at E18.5, suggesting delayed maturation of the interventricular septum   (MGI Ref ID J:192860)
  • reproductive system phenotype
  • decreased litter size
    • heterozygous females have small litters   (MGI Ref ID J:192860)

Ywhaetm1Awb/Ywhaetm1Awb

        either: 129S6/SvEvTac or (involves: 129S6/SvEvTac * NIH Black Swiss)
  • mortality/aging
  • partial perinatal lethality
    • most homozygotes died at birth   (MGI Ref ID J:84075)
    • 2.5% on mixed background survived   (MGI Ref ID J:84075)
    • 1% on inbred background survived   (MGI Ref ID J:84075)
    • survivors small but otherwise normal   (MGI Ref ID J:84075)
  • nervous system phenotype
  • abnormal brain morphology
    • increased apoptosis   (MGI Ref ID J:84075)
    • ventricular zone proliferation is normal   (MGI Ref ID J:84075)
    • abnormal cerebral cortex morphology
      • cortex is thinner than normal   (MGI Ref ID J:84075)
    • abnormal hippocampus pyramidal cell layer
      • pyramidal cell layer is disorganized and less cellular   (MGI Ref ID J:84075)
  • abnormal neuronal migration
    • neuronal migration distances for brain neurons are shorter than in wild-type   (MGI Ref ID J:84075)
  • cellular phenotype
  • abnormal neuronal migration
    • neuronal migration distances for brain neurons are shorter than in wild-type   (MGI Ref ID J:84075)

Ywhaetm1Awb/Ywhaetm1Awb

        involves: 129S6/SvEvTac
  • mortality/aging
  • complete perinatal lethality
    • die within 6 to 9 hours of birth   (MGI Ref ID J:192860)
  • homeostasis/metabolism phenotype
  • cyanosis
    • newborns exhibit cyanosis   (MGI Ref ID J:192860)
  • cardiovascular system phenotype
  • abnormal fetal cardiomyocyte physiology
    • embryonic cardiomyocytes display cell cycle defects characterized by a reduced number in G2/M and an accumulation in the G0/G1 phase   (MGI Ref ID J:192860)
    • decreased fetal cardiomyocyte proliferation
      • proliferation is decreased in E12.5 hearts and the mitotic index is 47% lower in whole hearts   (MGI Ref ID J:192860)
      • mitotic index is lower in the ventricles but not in the septum   (MGI Ref ID J:192860)
      • proliferation in the compact zone of the left ventricle is decreased   (MGI Ref ID J:192860)
  • abnormal heart morphology
    • increase in heart cavity diameter   (MGI Ref ID J:192860)
    • abnormal heart ventricle morphology
      • thinner ventricles at E12.5   (MGI Ref ID J:192860)
      • dilated heart ventricle
        • biventricular dilatation in E18.5 hearts   (MGI Ref ID J:192860)
      • thin ventricle myocardium compact layer
        • E12.5 mutants exhibit a reduction in ventricular compact myocardium thickness indicating ventricular non-compaction   (MGI Ref ID J:192860)
      • thin ventricular wall
        • thin biventricular walls at E18.5   (MGI Ref ID J:192860)
      • ventricular septal defect
        • 60% of mutants exhibit ventricular septal defects at E18.5   (MGI Ref ID J:192860)
    • abnormal myocardial trabeculae morphology
      • hearts display deep intertrabecular recesses   (MGI Ref ID J:192860)
    • thin myocardium compact layer
      • thinner compact myocardium at E12.5, with few cell layers forming the ventricular wall   (MGI Ref ID J:192860)
      • thin ventricle myocardium compact layer
        • E12.5 mutants exhibit a reduction in ventricular compact myocardium thickness indicating ventricular non-compaction   (MGI Ref ID J:192860)
  • cellular phenotype
  • abnormal cell cycle
    • embryonic cardiomyocytes display cell cycle defects characterized by a reduced number in G2/M and an accumulation in the G0/G1 phase   (MGI Ref ID J:192860)
    • decreased mitotic index
      • mitotic index in whole hearts is 47% lower than in controls and is also lower in the ventricles but not in the septum   (MGI Ref ID J:192860)
  • decreased fetal cardiomyocyte proliferation
    • proliferation is decreased in E12.5 hearts and the mitotic index is 47% lower in whole hearts   (MGI Ref ID J:192860)
    • mitotic index is lower in the ventricles but not in the septum   (MGI Ref ID J:192860)
    • proliferation in the compact zone of the left ventricle is decreased   (MGI Ref ID J:192860)
  • muscle phenotype
  • abnormal myocardial trabeculae morphology
    • hearts display deep intertrabecular recesses   (MGI Ref ID J:192860)
  • decreased fetal cardiomyocyte proliferation
    • proliferation is decreased in E12.5 hearts and the mitotic index is 47% lower in whole hearts   (MGI Ref ID J:192860)
    • mitotic index is lower in the ventricles but not in the septum   (MGI Ref ID J:192860)
    • proliferation in the compact zone of the left ventricle is decreased   (MGI Ref ID J:192860)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Cortical Defects
Neurodevelopmental Defects

Research Tools
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ywhaetm1Awb
Allele Name targeted mutation 1, Anthony Wynshaw-Boris
Allele Type Targeted (Null/Knockout)
Common Name(s) 14-3-3epsilon-; Ywhae-;
Strain of Origin129S6/SvEvTac
ES Cell Line NameTC1/TC-1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Ywhae, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide
Chromosome 11
Gene Common Name(s) 14-3-3 epsilon; 14-3-3E; AU019196; HEL2; KCIP-1; MDCR; MDS; expressed sequence AU019196;
Molecular Note Exons 2 and 3 were partially replaced by a neomycin resistance gene and a loxP site. Immunoblot analysis indicated the complete absence of gene product in homozygotes and a reduction by half in heterozygotes. [MGI Ref ID J:84075]

Genotyping

Genotyping Information

Genotyping Protocols

Ywhaetm1Awb STD PCR, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Toyo-oka K; Shionoya A; Gambello MJ; Cardoso C; Leventer R; Ward HL; Ayala R; Tsai LH; Dobyns W; Ledbetter D; Hirotsune S; Wynshaw-Boris A. 2003. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet 34(3):274-85. [PubMed: 12796778]  [MGI Ref ID J:84075]

Additional References

Ywhaetm1Awb related

Hippenmeyer S; Youn YH; Moon HM; Miyamichi K; Zong H; Wynshaw-Boris A; Luo L. 2010. Genetic mosaic dissection of lis1 and ndel1 in neuronal migration. Neuron 68(4):695-709. [PubMed: 21092859]  [MGI Ref ID J:166047]

Ikeda M; Hikita T; Taya S; Uraguchi-Asaki J; Toyo-oka K; Wynshaw-Boris A; Ujike H; Inada T; Takao K; Miyakawa T; Ozaki N; Kaibuchi K; Iwata N. 2008. Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia. Hum Mol Genet 17(20):3212-22. [PubMed: 18658164]  [MGI Ref ID J:139959]

Jafar-Nejad P; Ward CS; Richman R; Orr HT; Zoghbi HY. 2011. Regional rescue of spinocerebellar ataxia type 1 phenotypes by 14-3-3epsilon haploinsufficiency in mice underscores complex pathogenicity in neurodegeneration. Proc Natl Acad Sci U S A 108(5):2142-7. [PubMed: 21245341]  [MGI Ref ID J:169114]

Kosaka Y; Cieslik KA; Li L; Lezin G; Maguire CT; Saijoh Y; Toyo-oka K; Gambello MJ; Vatta M; Wynshaw-Boris A; Baldini A; Yost HJ; Brunelli L. 2012. 14-3-3epsilon plays a role in cardiac ventricular compaction by regulating the cardiomyocyte cell cycle. Mol Cell Biol 32(24):5089-102. [PubMed: 23071090]  [MGI Ref ID J:192860]

Pramparo T; Libiger O; Jain S; Li H; Youn YH; Hirotsune S; Schork NJ; Wynshaw-Boris A. 2011. Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects. PLoS Genet 7(3):e1001331. [PubMed: 21423666]  [MGI Ref ID J:171698]

Sekiguchi H; Iritani S; Habuchi C; Torii Y; Kuroda K; Kaibuchi K; Ozaki N. 2011. Impairment of the tyrosine hydroxylase neuronal network in the orbitofrontal cortex of a genetically modified mouse model of schizophrenia. Brain Res 1392:47-53. [PubMed: 21458426]  [MGI Ref ID J:172509]

Yingling J; Toyo-Oka K; Wynshaw-Boris A. 2003. Miller-Dieker syndrome: analysis of a human contiguous gene syndrome in the mouse. Am J Hum Genet 73(3):475-88. [PubMed: 12905154]  [MGI Ref ID J:85444]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as heterozygotes. Most homozygotes die at birth, less than 1% of homozygotes survive to adulthood.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   002448 129S1/SvImJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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