Description

Strain Information

Former Names B6.129P2-Mecp2tm2Bird/J    (Changed: 06-MAY-08 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System See Colony Maintenance Species laboratory mouse Generation N6+N5 (18-DEC-08)   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 (Mecp2^lox-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 by The Jackson Laboratory revealed that this strain is on a mixed B6;129 genetic background background.

Control Information

	Control
	Wild-type from the colony
	100492 B6129PF1/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mecp2

003890	B6.129P2(C)-Mecp2tm1.1Bird/J
007177	B6.129P2-Mecp2tm1Bird/J
005439	B6.129S-Mecp2tm1Hzo/J
006847	B6;129P2-Mecp2tm1Bird/J

View Strains carrying other alleles of Mecp2     (4 strains)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Rett Syndrome; RTT - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mecp2^tm2Bird/Mecp2⁺

        involves: 129P2/OlaHsd * C57BL/6

• behavior/neurological phenotype
• abnormal behavior (MGI Ref ID J:118365)
  • 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)
• limb grasping (MGI Ref ID J:118365)
  • at 4 to 12 months of age
• tremors (MGI Ref ID J:118365)
  • at 4 to 12 months of age
• growth/size phenotype
• obese (MGI Ref ID J:118365)
  • mice exhibit excess weight gain
• nervous system phenotype
• reduced long term potentiation (MGI Ref ID J:118365)
  • mice develop a reduction in long term potentiation
• respiratory system phenotype
• abnormal breathing (MGI Ref ID J:118365)
  • at 4 to 12 months of age

Mecp2^tm2Bird/Y

        involves: 129P2/OlaHsd * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:118365)
  • male mice survive on average 11 weeks from birth
• behavior/neurological phenotype
• abnormal behavior (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)
  • at 12 weeks mice display low stance, inertia, tremor, arrhythmic breathing, splayed himdlimb and moderate hindlimb clasping
• limb grasping (MGI Ref ID J:118365)
  • at 12 weeks, mice display moderate hindlimb clasping
• tremors (MGI Ref ID J:118365)
  • at 12 weeks
• respiratory system phenotype
• abnormal breathing (MGI Ref ID J:118365)
  • at 12 weeks

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

Mecp2^tm2Bird/Mecp2⁺ Tg(CAG-cre/Esr1)5Amc/?

        involves: 129P2/OlaHsd * C57BL/6 * CBA   (conditional)

• behavior/neurological phenotype
• abnormal behavior (MGI Ref ID J:118365)
  • 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)
  • however, tamoxifen treatment after the onset of symptoms reverses symptom progression
• limb grasping (MGI Ref ID J:118365)
  • at 4 to 12 months of age
  • however, tamoxifen treatment after the onset of symptoms reverses symptom progression
• tremors (MGI Ref ID J:118365)
  • at 4 to 12 months of age
  • however, tamoxifen treatment after the onset of symptoms reverses symptom progression
• nervous system phenotype
• reduced long term potentiation (MGI Ref ID J:118365)
  • mice develop a reduction in long term potentiation
  • however, treatment with tamoxifen returns long term potentiation to normal levels
• respiratory system phenotype
• abnormal breathing (MGI Ref ID J:118365)
  • at 4 to 12 months of age
  • however, tamoxifen treatment after the onset of symptoms reverses symptom progression
• growth/size phenotype
• obese (MGI Ref ID J:118365)
  • mice exhibit excess weight gain
  • however, tamoxifen treatment after the onset of symptoms reverses weight gain

Mecp2^tm2Bird/Y Tg(CAG-cre/Esr1)5Amc/0

        involves: 129P2/OlaHsd * C57BL/6 * CBA   (conditional)

• life span-post-weaning/aging
• premature death (MGI Ref ID J:118365)
  • 9 of 17 mice treated with tamoxifen at 3 to 4 weeks of age die soon after treatment
  • 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
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:118365)
  • the surviving 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age exhibit normal behavior/neurological phenotypes
• abnormal behavior (MGI Ref ID J:118365)
  • at 12 weeks mice display low stance, inertia, tremor, arrhythmic breathing, splayed himdlimb and moderate hindlimb clasping
  • 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)
  • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms
• limb grasping (MGI Ref ID J:118365)
  • at 12 weeks, mice display moderate hindlimb clasping
  • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms
• tremors (MGI Ref ID J:118365)
  • at 12 weeks
  • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms
• respiratory system phenotype
• abnormal breathing (MGI Ref ID J:118365)
  • at 12 weeks
  • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms

Genes & Alleles

Gene & Allele Information

Allele Symbol		Mecp2tm2Bird
Allele Name		targeted mutation 2, Adrian Bird
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Mecp2lox-stop;
Mutation Made By		Adrian Bird,   University of Edinburgh
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Mecp2, methyl CpG binding protein 2
Chromosome		X
Gene Common Name(s)		1500041B07Rik; AUTSX3; BB130002; D630021H01Rik; DKFZp686A24160; MRX16; MRX79; MRXS13; MRXSL; Mbd5; PPMX; RIKEN cDNA 1500041B07 gene; RIKEN cDNA D630021H01 gene; 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

Mecp2^tm2Bird, STD PCR, vers. 1
Mept2^tm2bird, MCA, vers. 1

Helpful Links

Genotyping resources and troubleshooting

References

References

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]

Mecp2^tm2Bird related

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]

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]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When 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 System	See above
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	100492 B6129PF1/J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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