Overview

Also Known As:Mecp2^lox-stop

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.

Donating Investigator

Adrian Bird, University of Edinburgh

Genetic overview

Genetic Background	Generation

Mecp2^tm2Bird

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Null/Knockout)	Mecp2	methyl CpG binding protein 2

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Research Applications

Research Tools
Neurobiology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 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 Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):1143-7PubMed: 17289941 MGI: J:118365

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Genetics

Mecp2^tm2Bird

Allele Symbol: Mecp2^tm2Bird

Allele Name	targeted mutation 2, Adrian Bird
Allele Type	Targeted (Conditional ready (e.g. floxed), Null/Knockout)
Allele Synonym(s)	Mecp2^lox-stop; Mecp2^stop
Gene Symbol and Name	Mecp2, methyl CpG binding protein 2
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	X
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.
Mutations Made By	Adrian Bird, University of Edinburgh

Disease/Phenotype

Disease Terms

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

Research Areas By Phenotype

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

Research Tools
- Developmental Biology Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
Neurobiology Research
- Behavioral and Learning Defects
- Neurodevelopmental Defects
  - Rett's syndrome
- Cre-lox System
  - loxP-flanked Sequences
Mouse/Human Gene Homologs
- Rett syndrome

Genotype: Mecp2^tm2Bird related

Neurobiology Research
- Ataxia (Movement) Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Mecp2^tm2Bird/Y
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

abnormal behavior
- 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)

limb grasping
- at 12 weeks, mice display moderate hindlimb clasping

tremors
- at 12 weeks

mortality/aging

premature death
- male mice survive on average 11 weeks from birth

respiratory system phenotype

abnormal breathing pattern
- at 12 weeks

Genotype: Mecp2^tm2Bird/Y Tg(CAG-cre/Esr1)5Amc/0
involves: 129P2/OlaHsd C57BL/6 * CBA

behavior/neurological phenotype

abnormal behavior
- 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
- 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
- at 12 weeks
- mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms

mortality/aging

premature death
- Normal - 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
- 9 of 17 mice treated with tamoxifen at 3 to 4 weeks of age die soon after treatment

respiratory system phenotype

abnormal breathing pattern
- at 12 weeks
- mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms

mammalian phenotype

behavior/neurological phenotype
- Normal - the surviving 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age exhibit normal behavior/neurological phenotypes

Genotype: Mecp2^tm2Bird/Mecp2⁺ Tg(CAG-cre/Esr1)5Amc/?
involves: 129P2/OlaHsd C57BL/6 * CBA

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)
- Normal - however, tamoxifen treatment after the onset of symptoms reverses symptom progression

limb grasping
- Normal - however, tamoxifen treatment after the onset of symptoms reverses symptom progression
- at 4 to 12 months of age

tremors
- Normal - however, tamoxifen treatment after the onset of symptoms reverses symptom progression
- at 4 to 12 months of age

respiratory system phenotype

abnormal breathing pattern
- Normal - however, tamoxifen treatment after the onset of symptoms reverses symptom progression
- at 4 to 12 months of age

growth/size/body region phenotype

obese
- mice exhibit excess weight gain
- Normal - however, tamoxifen treatment after the onset of symptoms reverses weight gain

nervous system phenotype

reduced long term potentiation
- Normal - however, treatment with tamoxifen returns long term potentiation to normal levels
- mice develop a reduction in long term potentiation

Genotype: Mecp2^tm2Bird/Mecp2⁺
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

tremors
- at 4 to 12 months of age

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)

limb grasping
- at 4 to 12 months of age

growth/size/body region phenotype

obese
- mice exhibit excess weight gain

nervous system phenotype

reduced long term potentiation
- mice develop a reduction in long term potentiation

respiratory system phenotype

abnormal breathing pattern
- at 4 to 12 months of age

Genotype: Chat^tm2(cre)Lowl/Chat⁺ Mecp2^tm2Bird/Y
involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J

mammalian phenotype

cardiovascular system phenotype
- Normal - mice exhibit a regular heart rate and show rescue of spontaneous and induced cardiac arrhythmias, long QT, and improved survival

homeostasis/metabolism phenotype
- Normal - mice exhibit a regular body temperature

behavior/neurological phenotype
- Normal - mice exhibit normal activity

respiratory system phenotype

apnea

abnormal respiration
- abnormal hypoxic breathing response

The following phenotype relates to a compound genotype created using this strain

Genotype: Mecp2^tm2Bird/Y
B6.129P2-Mecp2/J

mortality/aging

premature death
- mice die prematurely with a median survival of 16 weeks
- 2 of 7 mice exhibit sudden death

respiratory system phenotype

abnormal respiration
- abnormal hypoxic breathing response

apnea

cardiovascular system phenotype

atrioventricular block
- an increase in sinus pauses and atrioventricular block events are seen up until 13 hours before death, but once heart rate drops to the bradycardic level, these arrhythmias cease

increased heart rate variability
- increase in heart rate variability during the dark cycle

prolonged QT interval

increased response of heart to induced stress
- mice show increased susceptibility to induction of arrhythmias

abnormal heart rate
- abnormal fluctuations in heart rate in mice that die suddenly

ventricular premature beat
- mice exhibit a higher incidence of sinus pauses and premature ventricular contractions

abnormal heartbeat
- irregular heart rhythm with sudden bradycardic events

decreased heart rate
- heart rate declines dramatically to severe bradycardia before death

homeostasis/metabolism phenotype

decreased body temperature
- decreased body temperature during both the light and dark cycle

increased response of heart to induced stress
- mice show increased susceptibility to induction of arrhythmias

References

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):1143-7PubMed: 17289941 MGI: 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):E10PubMed: 11160912 MGI: J:111323

Additional - Mecp2^tm2Bird related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Mecp2
- Separated PCR:Mept2
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the Mecp2^lox-stop mouse strain in a publication, please cite the originating article(s) and include JAX stock #006849 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	X linked - Heterozygous Females and Wild-type Males for Mecp2<tm2Bird> 2 pair minimum

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Mecp2lox-stop

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Mecp2tm2Bird

Allele Symbol: Mecp2tm2Bird

Disease Terms

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).

Research Areas By Phenotype

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

Genotype: Mecp2tm2Bird related

Mammalian Phenotype Terms by Genotype

Genotype: Mecp2tm2Bird/Yinvolves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

mortality/aging

respiratory system phenotype

Genotype: Mecp2tm2Bird/Y Tg(CAG-cre/Esr1*)5Amc/0involves: 129P2/OlaHsd * C57BL/6 * CBA

behavior/neurological phenotype

mortality/aging

respiratory system phenotype

mammalian phenotype

Genotype: Mecp2tm2Bird/Mecp2+ Tg(CAG-cre/Esr1*)5Amc/?involves: 129P2/OlaHsd * C57BL/6 * CBA

behavior/neurological phenotype

respiratory system phenotype

growth/size/body region phenotype

nervous system phenotype

Genotype: Mecp2tm2Bird/Mecp2+involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

nervous system phenotype

respiratory system phenotype

Genotype: Chattm2(cre)Lowl/Chat+ Mecp2tm2Bird/Yinvolves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J

mammalian phenotype

respiratory system phenotype

Genotype: Mecp2tm2Bird/YB6.129P2-Mecp2/J

mortality/aging

respiratory system phenotype

cardiovascular system phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Mecp2tm2Bird related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:Mecp2^lox-stop

Mecp2^tm2Bird

Allele Symbol: Mecp2^tm2Bird

Genotype: Mecp2^tm2Bird related

Genotype: Mecp2^tm2Bird/Y
involves: 129P2/OlaHsd * C57BL/6

Genotype: Mecp2^tm2Bird/Y Tg(CAG-cre/Esr1)5Amc/0
involves: 129P2/OlaHsd C57BL/6 * CBA

Genotype: Mecp2^tm2Bird/Mecp2⁺ Tg(CAG-cre/Esr1)5Amc/?
involves: 129P2/OlaHsd C57BL/6 * CBA

Genotype: Mecp2^tm2Bird/Mecp2⁺
involves: 129P2/OlaHsd * C57BL/6

Genotype: Chat^tm2(cre)Lowl/Chat⁺ Mecp2^tm2Bird/Y
involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J

Genotype: Mecp2^tm2Bird/Y
B6.129P2-Mecp2/J

Additional - Mecp2^tm2Bird related