Strain Name:

B6.129P2-Mecp2tm2Bird/J

Stock Number:

006849

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Mice with this X-linked lox-STOP mutation of the methyl CpG binding protein 2 gene may be useful in neurological and developmental studies of Rett syndrome and its amelioration upon excision of the lox-STOP cassette.

Description

Strain Information

Former Names B6;129P2-Mecp2tm2Bird/J    (Changed: 16-SEP-09 )
B6.129P2-Mecp2tm2Bird/J    (Changed: 06-MAY-08 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemSee Colony Maintenance under the Health & Care tab         (Female x Male)   20-FEB-09
Specieslaboratory mouse
GenerationN6+N18 (13-DEC-13)
Generation Definitions
 
Donating Investigator Adrian Bird,   University of Edinburgh

Description
These mice possess a loxP-flanked STOP cassette in intron 2 of the targeted gene on the X chromosome. Western blot and hybridization analysis confirm the absence of wildtype protein from the targeted allele (although the donating investigator reports that the targeted allele produces a "read-through" transcript which does not give rise to detectable levels of protein but makes it difficult to discriminate between the "flox-stopped" and reactivated alleles by RT-PCR). Hemizygous (Mecp2lox-Stop/y) males do not breed and develop Rett syndrome symptoms (reduced mobility, hindlimb clasping) at approximately 6 weeks of age, with death occurring at approximately 11 weeks of age. Heterozygous females are fertile until developing Rett syndrome characteristics at 4-12 months of age. This Rett syndrome-like phenotype is similar to that observed for the traditional knock-out allele (see Stock No. 003890). Cre recombinase-mediated removal of the floxed-STOP cassette restores transcription from the targeted allele and MECP2 protein activity to normal, and reverses the Rett syndrome-like neurological defects.

This mutant mouse strain may be bred to a strain expressing tamoxifen inducible Cre recombinase in most tissues (see Stock No. 004682).

Mice with this X-linked lox-STOP mutation may be useful in neurological and developmental studies of Rett syndrome and its amelioration upon excision of the lox-STOP cassette.

Development
A targeting vector was designed to insert a loxP-flanked STOP-Neo cassette into intron 2 of the targeted gene. The STOP-Neo cassette is composed of a PGK-Neo cassette followed by the 3' portion of the yeast His3 gene, an SV40 polyadenylation sequence, and a false translation initiation codon followed by a 5' splice donor site. The construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric offspring were bred to C57BL/6 mice. Heterozygous female mutants were bred to wild-type C57BL/6 males for 5 generations prior to arrival at The Jackson Laboratory. A SNP (single nucleotide polymorphism) panel analysis performed in April 2009 by The Jackson Laboratory revealed that this strain was on a mixed B6;129 genetic background background. Further backcrossing to C57BL/6J inbred mice generated mutant mice congenic on a C57BL/6 genetic background (confirmed by SNP analysis August 2009).

Control Information

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

Related Strains

View Strains carrying other alleles of Mecp2     (10 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Rett Syndrome; RTT
- Potential model based on gene homology relationships. 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)
Lubs X-Linked Mental Retardation Syndrome; MRXSL   (MECP2)
Mental Retardation, X-Linked, Syndromic 13; MRXS13   (MECP2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Mecp2tm2Bird/Mecp2+

        involves: 129P2/OlaHsd * C57BL/6
  • behavior/neurological phenotype
  • abnormal behavior
    • at 4 to 12 months of age, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition)   (MGI Ref ID J:118365)
    • limb grasping
      • at 4 to 12 months of age   (MGI Ref ID J:118365)
    • tremors
      • at 4 to 12 months of age   (MGI Ref ID J:118365)
  • growth/size/body phenotype
  • obese
    • mice exhibit excess weight gain   (MGI Ref ID J:118365)
  • nervous system phenotype
  • reduced long term potentiation
    • mice develop a reduction in long term potentiation   (MGI Ref ID J:118365)
  • respiratory system phenotype
  • abnormal breathing pattern
    • at 4 to 12 months of age   (MGI Ref ID J:118365)

Mecp2tm2Bird/Y

        involves: 129P2/OlaHsd * C57BL/6
  • mortality/aging
  • premature death
    • male mice survive on average 11 weeks from birth   (MGI Ref ID J:118365)
  • behavior/neurological phenotype
  • abnormal behavior
    • during the last 4 weeks of life, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition)   (MGI Ref ID J:118365)
    • at 12 weeks mice display low stance, inertia, tremor, arrhythmic breathing, splayed himdlimb and moderate hindlimb clasping   (MGI Ref ID J:118365)
    • limb grasping
      • at 12 weeks, mice display moderate hindlimb clasping   (MGI Ref ID J:118365)
    • tremors
  • respiratory system phenotype
  • abnormal breathing pattern

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Mecp2tm2Bird/Mecp2+ Tg(CAG-cre/Esr1*)5Amc/?

        involves: 129P2/OlaHsd * C57BL/6 * CBA   (conditional)
  • behavior/neurological phenotype
  • abnormal behavior
    • at 4 to 12 months of age, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition)   (MGI Ref ID J:118365)
    • however, tamoxifen treatment after the onset of symptoms reverses symptom progression   (MGI Ref ID J:118365)
    • limb grasping
      • at 4 to 12 months of age   (MGI Ref ID J:118365)
      • however, tamoxifen treatment after the onset of symptoms reverses symptom progression   (MGI Ref ID J:118365)
    • tremors
      • at 4 to 12 months of age   (MGI Ref ID J:118365)
      • however, tamoxifen treatment after the onset of symptoms reverses symptom progression   (MGI Ref ID J:118365)
  • nervous system phenotype
  • reduced long term potentiation
    • mice develop a reduction in long term potentiation   (MGI Ref ID J:118365)
    • however, treatment with tamoxifen returns long term potentiation to normal levels   (MGI Ref ID J:118365)
  • respiratory system phenotype
  • abnormal breathing pattern
    • at 4 to 12 months of age   (MGI Ref ID J:118365)
    • however, tamoxifen treatment after the onset of symptoms reverses symptom progression   (MGI Ref ID J:118365)
  • growth/size/body phenotype
  • obese
    • mice exhibit excess weight gain   (MGI Ref ID J:118365)
    • however, tamoxifen treatment after the onset of symptoms reverses weight gain   (MGI Ref ID J:118365)

Mecp2tm2Bird/Y Tg(CAG-cre/Esr1*)5Amc/0

        involves: 129P2/OlaHsd * C57BL/6 * CBA   (conditional)
  • mortality/aging
  • premature death
    • 9 of 17 mice treated with tamoxifen at 3 to 4 weeks of age die soon after treatment   (MGI Ref ID J:118365)
    • however, tamoxifen-tocixity is not responsible for observed deaths, 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age have a normal life span, and mice treated with tamoxifen from week 12 to 17 exhibit normal lethality   (MGI Ref ID J:118365)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • the surviving 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age exhibit normal behavior/neurological phenotypes   (MGI Ref ID J:118365)
    • abnormal behavior
      • at 12 weeks mice display low stance, inertia, tremor, arrhythmic breathing, splayed himdlimb and moderate hindlimb clasping   (MGI Ref ID J:118365)
      • during the last 4 weeks of life, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition)   (MGI Ref ID J:118365)
      • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms   (MGI Ref ID J:118365)
      • limb grasping
        • at 12 weeks, mice display moderate hindlimb clasping   (MGI Ref ID J:118365)
        • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms   (MGI Ref ID J:118365)
      • tremors
        • at 12 weeks   (MGI Ref ID J:118365)
        • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms   (MGI Ref ID J:118365)
  • respiratory system phenotype
  • abnormal breathing pattern
    • at 12 weeks   (MGI Ref ID J:118365)
    • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms   (MGI Ref ID J:118365)
View Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
Cre-lox System
      loxP-flanked Sequences
Neurodevelopmental Defects
      Rett's syndrome

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System

Mecp2tm2Bird related

Neurobiology Research
Ataxia (Movement) Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mecp2tm2Bird
Allele Name targeted mutation 2, Adrian Bird
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Mecp2lox-stop; Mecp2stop;
Mutation Made By Adrian Bird,   University of Edinburgh
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14TG2a
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Mecp2, methyl CpG binding protein 2
Chromosome X
Gene Common Name(s) 1500041B07Rik; AUTSX3; BB130002; D630021H01Rik; MRX16; MRX79; MRXS13; MRXSL; Mbd5; PPMX; RIKEN cDNA 1500041B07 gene; RIKEN cDNA D630021H01 gene; RS; RTS; RTT; WBP10; expressed sequence BB130002;
Molecular Note Cre recombinase-reversible gene inactivation was accomplished by insertion into intron 2 of a 3.1-kb DNA fragment containing a loxP-flanked "neostop" cassette, which comprises a neomycin resistance cassette followed by a transcriptional/translational "stop" cassette composed of 550 bp of 3' sequence from the Saccharomyces cerevisiae His3 gene, an SV40 polyadenylation sequence, and a synthetic sequence containing a false translation initiation codon (ATG) immediately followed by a consensus splice donor sequence. Despite the production of a read-through transcript, no protein product was detected by western blot or immunofluorescence analysis of brains of mutant mice. [MGI Ref ID J:111323] [MGI Ref ID J:118365] [MGI Ref ID J:75205]

Genotyping

Genotyping Information

Genotyping Protocols

Mept2tm2bird,

MELT


Mecp2tm2Bird, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Guy J; Gan J; Selfridge J; Cobb S; Bird A. 2007. Reversal of neurological defects in a mouse model of Rett syndrome. Science 315(5815):1143-7. [PubMed: 17289941]  [MGI Ref ID J:118365]

Additional References

Dragatsis I; Zeitlin S. 2001. A method for the generation of conditional gene repair mutations in mice. Nucleic Acids Res 29(3):E10. [PubMed: 11160912]  [MGI Ref ID J:111323]

Mecp2tm2Bird related

De Felice C; Della Ragione F; Signorini C; Leoncini S; Pecorelli A; Ciccoli L; Scalabri F; Marracino F; Madonna M; Belmonte G; Ricceri L; De Filippis B; Laviola G; Valacchi G; Durand T; Galano JM; Oger C; Guy A; Bultel-Ponce V; Guy J; Filosa S; Hayek J; D'Esposito M. 2014. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome. Neurobiol Dis 68:66-77. [PubMed: 24769161]  [MGI Ref ID J:214008]

Derecki NC; Cronk JC; Lu Z; Xu E; Abbott SB; Guyenet PG; Kipnis J. 2012. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484(7392):105-9. [PubMed: 22425995]  [MGI Ref ID J:183878]

Dragatsis I; Zeitlin S. 2001. A method for the generation of conditional gene repair mutations in mice. Nucleic Acids Res 29(3):E10. [PubMed: 11160912]  [MGI Ref ID J:111323]

Durand S; Patrizi A; Quast KB; Hachigian L; Pavlyuk R; Saxena A; Carninci P; Hensch TK; Fagiolini M. 2012. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2. Neuron 76(6):1078-90. [PubMed: 23259945]  [MGI Ref ID J:197657]

Goffin D; Brodkin ES; Blendy JA; Siegel SJ; Zhou Z. 2014. Cellular origins of auditory event-related potential deficits in Rett syndrome. Nat Neurosci 17(6):804-6. [PubMed: 24777420]  [MGI Ref ID J:212933]

Kernohan KD; Jiang Y; Tremblay DC; Bonvissuto AC; Eubanks JH; Mann MR; Berube NG. 2010. ATRX partners with cohesin and MeCP2 and contributes to developmental silencing of imprinted genes in the brain. Dev Cell 18(2):191-202. [PubMed: 20159591]  [MGI Ref ID J:158584]

Lakso M; Sauer B; Mosinger B Jr; Lee EJ; Manning RW; Yu SH; Mulder KL; Westphal H. 1992. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc Natl Acad Sci U S A 89(14):6232-6. [PubMed: 1631115]  [MGI Ref ID J:75205]

Lang M; Wither RG; Brotchie JM; Wu C; Zhang L; Eubanks JH. 2013. Selective preservation of MeCP2 in catecholaminergic cells is sufficient to improve the behavioral phenotype of male and female Mecp2-deficient mice. Hum Mol Genet 22(2):358-71. [PubMed: 23077217]  [MGI Ref ID J:191128]

Lang M; Wither RG; Colic S; Wu C; Monnier PP; Bardakjian BL; Zhang L; Eubanks JH. 2014. Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation. Hum Mol Genet 23(2):303-18. [PubMed: 24009314]  [MGI Ref ID J:204519]

Lioy DT; Garg SK; Monaghan CE; Raber J; Foust KD; Kaspar BK; Hirrlinger PG; Kirchhoff F; Bissonnette JM; Ballas N; Mandel G. 2011. A role for glia in the progression of Rett's syndrome. Nature 475(7357):497-500. [PubMed: 21716289]  [MGI Ref ID J:174777]

McLeod F; Ganley R; Williams L; Selfridge J; Bird A; Cobb SR. 2013. Reduced seizure threshold and altered network oscillatory properties in a mouse model of Rett syndrome. Neuroscience 231:195-205. [PubMed: 23238573]  [MGI Ref ID J:194298]

Nguyen MV; Felice CA; Du F; Covey MV; Robinson JK; Mandel G; Ballas N. 2013. Oligodendrocyte lineage cells contribute unique features to Rett syndrome neuropathology. J Neurosci 33(48):18764-74. [PubMed: 24285883]  [MGI Ref ID J:204155]

Robinson L; Plano A; Cobb S; Riedel G. 2013. Long-term home cage activity scans reveal lowered exploratory behaviour in symptomatic female Rett mice. Behav Brain Res 250:148-56. [PubMed: 23643691]  [MGI Ref ID J:198941]

Ward CS; Arvide EM; Huang TW; Yoo J; Noebels JL; Neul JL. 2011. MeCP2 Is Critical within HoxB1-Derived Tissues of Mice for Normal Lifespan. J Neurosci 31(28):10359-70. [PubMed: 21753013]  [MGI Ref ID J:174516]

Weng SM; McLeod F; Bailey ME; Cobb SR. 2011. Synaptic plasticity deficits in an experimental model of rett syndrome: long-term potentiation saturation and its pharmacological reversal. Neuroscience 180:314-21. [PubMed: 21296130]  [MGI Ref ID J:173701]

Wither RG; Lang M; Zhang L; Eubanks JH. 2013. Regional MeCP2 expression levels in the female MeCP2-deficient mouse brain correlate with specific behavioral impairments. Exp Neurol 239:49-59. [PubMed: 23022455]  [MGI Ref ID J:196997]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, females heterozygous for this X-linked mutation can be bred with wildtype male siblings. The donating investigator recommends replacing heterozygous female breeders when Rett syndrome symptoms appear or when females fail to produce or care for regular litters (may be as early as 4-6 months). The donating investigator also reports that breeding performance may be improved if mice are maintained on a mixed C57BL/6;BALB/c background.
Mating SystemSee Colony Maintenance under the Health & Care tab         (Female x Male)   20-FEB-09
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00MaleHemizygous for Mecp2tm2Bird  
$239.00FemaleHeterozygous for Mecp2tm2Bird  
Price per Pair (US dollars $)Pair Genotype
$311.00Heterozygous for Mecp2tm2Bird x Wild-type for Mecp2tm2Bird  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70MaleHemizygous for Mecp2tm2Bird  
$310.70FemaleHeterozygous for Mecp2tm2Bird  
Price per Pair (US dollars $)Pair Genotype
$404.30Heterozygous for Mecp2tm2Bird x Wild-type for Mecp2tm2Bird  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

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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