Strain Name:

B6.Cg-Mapttm1(Mecp2)Jae/LimmJ

Stock Number:

018282

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The Tau-MeCP2 knockin allele replaces endogenous microtubule-associated protein tau gene expression with Tau-MeCP2 fusion protein expression. Homozygous Tau-MeCP2 knockin mice recapitulate many key phenotypes of MECP2 duplication syndrome in humans. They may also be used for neuron-specific MeCP2 expression to rescue the Rett syndrome phenotype of other MeCP2 mutant mice.

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 Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating Investigator Lisa M Monteggia,   Univ of Texas Southwest Med Ctr Dallas

Description
The Tau-MeCP2 knockin mutation places the mouse MeCP2 cDNA sequence into exon 1 of the tau gene, in-frame with the endogenous tau start codon. Under control of the endogenous tau promoter/enhancer sequences, expression of the Tau-MeCP2 fusion protein (containing the first 31 amino acids of tau fused to the MeCP2 protein) is high in lung and kidney, low in heart, and very low in liver and spleen. Endogenous tau expression is abolished in the Tau-MeCP2 knockin allele. The axonal localization signal of tau is located in the 3' UTR, and therefore is not part of the Tau-MeCP2 mRNA. The onset of fusion protein expression correlates closely with endogenous tau expression (first detectable at 10.5 days post coitum [dpc]). While the amount of Mecp2 RNA is similar to Tau-MeCP2 RNA in heterozygous Tau-MeCP2 mice embryos and adult brain, the fusion protein expression level is approximately two-to-four times more abundant; suggesting a difference in either translation efficiency of the transcripts or protein stability. As such, the Tau-MeCP2 knockin results in MeCP2 overexpression directed primarily to heterochromatic foci of post-mitotic neurons in the brain. Heterozygous Tau-MeCP2 knockin mice tolerate ~2-3 fold MeCP2 overexpression levels in brain with no adverse effects on viability or fertility. By 3-5 months of age, heterozygotes display impaired motor coordination, heightened anxiety, and impaired learning and memory (accompanied by deficits in long-term potentiation and short-term synaptic plasticity). Mice homozygous for the Tau-MeCP2 knockin allele have ~4-6 fold MeCP2 overexpression levels in brain, resulting in a profound motor dysfunction with side-to-side swaying, tremors, and gait ataxia. Homozygotes are severely runted by weaning age (failure to thrive largely caused by inability to compete with littermates for food), remain smaller than wildtype mice, and fail to mate. The donating investigator (Dr. Lisa M. Monteggia) suggests using heterozygous mice for assessing behavioral traits, as the homozygous phenotype may complicate the analysis of behavioral testing.

Development
The pTAU-MeCP2pAneo targeting vector was designed by Dr. Rudolf Jaenisch (Whitehead Institute MIT) to insert the mouse methyl CpG binding protein 2 (Mecp2) coding sequence, an SV40 late polyadenylation signal, and a PGK-neomycin resistance cassette as an in-frame fusion into exon 1 of the microtubule-associated protein tau locus (Mapt). The 1455 nucleotide MeCP2 cDNA sequence was obtained via PCR amplification of IMAGE clone 1395411 isolated from a C57BL/6 male mouse (GenBank accession no. AI181668). The targeting vector was electroporated into (C57BL/6 x 129S4/SvJae)F1-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient (DBA/2 x C57BL/6)F1 blastocysts. Chimeric males were bred with C57BL/6 females to generate the Tau-MeCP2 knockin colony. Heterozygous (Tau-MeCP2 ki/+) mice were backcrossed with C57BL/6J mice more than ten generations. In 2006, Dr. Jaenisch sent black heterozygous females to Dr. Lisa M. Monteggia (The University of Texas Southwestern Medical Center). There, the colony was maintained by breeding heterozygous females with wildtype sibling males and/or with C57BL/6J males for several generations. In 2012, Dr. Monteggia sent heterozygous males to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish The Jackson Laboratory Repository colony.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Mapt     (13 strains)

View Strains carrying other alleles of Mecp2     (10 strains)

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).
Lubs X-Linked Mental Retardation Syndrome; MRXSL
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Frontotemporal Dementia; FTD   (MAPT)
Parkinson Disease, Late-Onset; PD   (MAPT)
Parkinson-Dementia Syndrome   (MAPT)
Pick Disease of Brain   (MAPT)
Supranuclear Palsy, Progressive, 1; PSNP1   (MAPT)
- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Angelman Syndrome; AS   (MECP2)
Autism, Susceptibility to, X-Linked 3; AUTSX3   (MECP2)
Encephalopathy, Neonatal Severe, Due to Mecp2 Mutations   (MECP2)
Mental Retardation, X-Linked, Syndromic 13; MRXS13   (MECP2)
Rett Syndrome; RTT   (MECP2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Mapttm1(Mecp2)Jae/Mapttm1(Mecp2)Jae

        B6.Cg-Mapttm1(Mecp2)Jae
  • growth/size/body phenotype
  • decreased body weight   (MGI Ref ID J:182685)
  • nervous system phenotype
  • abnormal miniature excitatory postsynaptic currents
    • hippocampal neurons exhibit enhanced miniature excitatory neurotransmission; hippocampal neurons show an increase in mEPSC frequency with no change in mEPSC amplitude   (MGI Ref ID J:182685)
  • enhanced paired-pulse facilitation
    • paired-pulse facilitation is augmented in mutants at the interstimulus intervals of 30 and 50 ms   (MGI Ref ID J:182685)
  • reduced long term potentiation
    • high frequency stimulation-induced long term potentiation is attenuated in hippocampal slices from mutants compared to wild-type mice   (MGI Ref ID J:182685)
  • behavior/neurological phenotype
  • abnormal associative learning
    • mutants display consistent freezing levels across all extinction trials, indicating impaired extinction learning   (MGI Ref ID J:182685)
    • abnormal contextual conditioning behavior
      • mutants exhibit an increase in freezing behavior in context (novel environment)-dependent fear conditioning 24 hours after training, suggesting enhanced associative learning   (MGI Ref ID J:182685)
    • abnormal cued conditioning behavior
      • mutants exhibit an increase in freezing behavior in cue (auditory tone)-dependent fear conditioning 24 hours after training, suggesting enhanced associative learning   (MGI Ref ID J:182685)
      • however, mutants are incapable of extinguishing their conditioned response (freezing) to cue when cue is presented alone (without shock), indicating severe impairments in extinction learning and associative learning   (MGI Ref ID J:182685)
      • mutants do not show enhanced freezing behavior in the absence of a paired stimulus (baseline freezing) or before the tone in cued fear conditioning, suggesting that mutants learn to associate the cue with the shock   (MGI Ref ID J:182685)
  • abnormal object recognition memory
    • in the NOR task to test ability to recognize a novel object, mutants spend less time with the novel object than wild-type mice and show less preference for the novel object over the familiar indicating impaired episodic memory   (MGI Ref ID J:182685)
  • impaired coordination
    • mutants spend less time on the rotarod than wild-type mice   (MGI Ref ID J:182685)
  • increased anxiety-related response
    • in the elevated plus maze, mutants spend less time in the center, more time in the closed arms, and less time in the open arms compared with wild-type   (MGI Ref ID J:182685)
    • in the dark/light test, mutants spend less time in the light side and more time in the dark side, indicating heightened anxiety   (MGI Ref ID J:182685)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Mapttm1(Mecp2)Jae/Mapt+

        involves: 129/Sv * C57BL/6
  • normal phenotype
  • no abnormal phenotype detected
    • heterozygous mice are fertile and healthy with no obvious abnormalities   (MGI Ref ID J:89593)

Mapttm1(Mecp2)Jae/Mapttm1(Mecp2)Jae

        involves: 129/Sv * C57BL/6
  • mortality/aging
  • *normal* mortality/aging
    • no premature death is seen in homozygotes   (MGI Ref ID J:89593)
  • behavior/neurological phenotype
  • abnormal sexual interaction
    • homozygotes do not mate   (MGI Ref ID J:89593)
  • ataxia
    • gait ataxia is seen in homozygous mutants   (MGI Ref ID J:89593)
  • excessive scratching
    • lesions are seen by 9 months probably as a result of excessive scratching   (MGI Ref ID J:89593)
  • impaired balance
    • homozygotes display side-to-side swaying   (MGI Ref ID J:89593)
  • tremors   (MGI Ref ID J:89593)
  • growth/size/body phenotype
  • cachexia
    • by 9 months homozygotes appear emaciated   (MGI Ref ID J:89593)
  • postnatal growth retardation
    • by weaning homozygotes are 60% smaller than wild-type littermates probably as a result of an inability to compete for food   (MGI Ref ID J:89593)
    • after weaning homozygotes remain smaller than wild-type littermates   (MGI Ref ID J:89593)
  • vision/eye phenotype
  • cataracts
    • by 9 months homozygotes have developed cataracts   (MGI Ref ID J:89593)
  • integument phenotype
  • disheveled coat
    • by 9 months homozygotes appear disheveled   (MGI Ref ID J:89593)
View Research Applications

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

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Alzheimer's Disease
      Tau (Mapt) mutants
Ataxia (Movement) Defects
Behavioral and Learning Defects
      high anxiety
Neurodegeneration
Neurodevelopmental Defects
      Rett's syndrome
Tremor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mapttm1(Mecp2)Jae
Allele Name targeted mutation 1, Rudolf Jaenisch
Allele Type Targeted
Common Name(s) Tau-Mecp2 ki;
Mutation Made ByDr. Rudolf Jaenisch,   Whitehead Institute (MIT)
Strain of Origin(C57BL/6 x 129S4/SvJae)F1
Expressed Gene Mecp2, methyl CpG binding protein 2, mouse, laboratory
Gene Symbol and Name Mapt, microtubule-associated protein tau
Chromosome 11
Gene Common Name(s) AI413597; AW045860; DDPAC; FTDP-17; MAPTL; MSTD; MTBT1; MTBT2; Mtapt; PPND; PPP1R103; RNPTAU; TAU; Tau; expressed sequence AI413597; expressed sequence AW045860; pTau;
Molecular Note The mouse Mecp2 coding sequence, a modified Kozak sequence and a neo-cassette were placed in-frame into exon 1 of Mapt via homologous combination. The resulting fusion protein contained the first 31 amino acids of Mapt fused to Mecp2 and was highly expressed in the brain (in post-mitotic neurons), lung, and kidney. [MGI Ref ID J:89593]
 

Genotyping

Genotyping Information

Genotyping Protocols

Mapttm1(Mecp2)Jae, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Luikenhuis S; Giacometti E; Beard CF; Jaenisch R. 2004. Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci U S A 101(16):6033-8. [PubMed: 15069197]  [MGI Ref ID J:89593]

Na ES; Nelson ED; Adachi M; Autry AE; Mahgoub MA; Kavalali ET; Monteggia LM. 2012. A mouse model for MeCP2 duplication syndrome: MeCP2 overexpression impairs learning and memory and synaptic transmission. J Neurosci 32(9):3109-17. [PubMed: 22378884]  [MGI Ref ID J:182685]

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, heterozygous mice may be bred with wildtype mice from the colony or with C57BL/6J inbred mice. Homozygous mice exhibit profound motor, learning, and behavioral abnormalities, and the donating investigator reports that homozygous mice do not mate.

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* $2140.00
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* $2782.00
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
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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