JAX Mouse Strain Datasheet - 006849

B6.129P2-Mecp2^tm2Bird/J

Stock No:: 006849 |; Mecp2^lox-stop

Repository Live

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
	N6+N25 (13-APR-16)

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

Neurobiology Research
Research Tools

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Base Price

Starting at:

$224.00 Domestic price for female

$298.00 Domestic price for breeder pair

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

View All References

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)	1500041B07Rik; 1500041B07Rik; AUTSX3; BB130002; D630021H01Rik; D630021H01Rik; MRX16; MRX79; MRXS13; MRXSL; Mbd5; PPMX; RIKEN cDNA 1500041B07 gene; RIKEN cDNA D630021H01 gene; RS; RTS; RTT; WBP10; expressed sequence BB130002
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

Research Areas By Genotype

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

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/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)

limb grasping
- at 4 to 12 months of age

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

mortality/aging

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

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

respiratory system phenotype

abnormal breathing pattern
- at 12 weeks

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

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

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

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

respiratory system phenotype

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

growth/size/body region phenotype

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

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

mortality/aging

premature death
- 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

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

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

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

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

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):1143-7. PubMed: 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):E10. PubMed: 11160912 MGI: J:111323

Additional - Mecp2^tm2Bird related

Cortelazzo A; De Felice C; Guerranti R; Signorini C; Leoncini S; Pecorelli A; Scalabri F; Madonna M; Filosa S; Della Giovampaola C; Capone A; Durand T; Mirasole C; Zolla L; Valacchi G; Ciccoli L; Guy J; D'Esposito M; Hayek J. 2016. Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. Neurosci Res 105:28-34. PubMed: 26476268 MGI: J:231839
Cronk JC; Derecki NC; Ji E; Xu Y; Lampano AE; Smirnov I; Baker W; Norris GT; Marin I; Coddington N; Wolf Y; Turner SD; Aderem A; Klibanov AL; Harris TH; Jung S; Litvak V; Kipnis J. 2015. Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli. Immunity 42(4):679-91. PubMed: 25902482 MGI: J:229774
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: 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: 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: 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: J:197657
Gadalla KK; Ross PD; Riddell JS; Bailey ME; Cobb SR. 2014. Gait analysis in a Mecp2 knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits. PLoS One 9(11):e112889. PubMed: 25392929 MGI: J:225153
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: J:212933
Huang TW; Kochukov MY; Ward CS; Merritt J; Thomas K; Nguyen T; Arenkiel BR; Neul JL. 2016. Progressive Changes in a Distributed Neural Circuit Underlie Breathing Abnormalities in Mice Lacking MeCP2. J Neurosci 36(20):5572-86. PubMed: 27194336 MGI: J:231950
Kamal B; Russell D; Payne A; Constante D; Tanner KE; Isaksson H; Mathavan N; Cobb SR. 2015. Biomechanical properties of bone in a mouse model of Rett syndrome. Bone 71:106-14. PubMed: 25445449 MGI: J:219301
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: 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: 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: 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: 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: J:174777
Lombardi LM; Baker SA; Zoghbi HY. 2015. MECP2 disorders: from the clinic to mice and back. J Clin Invest 125(8):2914-23. PubMed: 26237041 MGI: J:225796
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: J:194298
Meng X; Wang W; Lu H; He LJ; Chen W; Chao ES; Fiorotto ML; Tang B; Herrera JA; Seymour ML; Neul JL; Pereira FA; Tang J; Xue M; Zoghbi HY. 2016. Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders. Elife 5:. PubMed: 27328325 MGI: J:234270
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: J:204155
Orefice LL; Zimmerman AL; Chirila AM; Sleboda SJ; Head JP; Ginty DD. 2016. Peripheral Mechanosensory Neuron Dysfunction Underlies Tactile and Behavioral Deficits in Mouse Models of ASDs. Cell :. PubMed: 27293187 MGI: J:232023
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: J:198941
Ross PD; Guy J; Selfridge J; Kamal B; Bahey N; Tanner KE; Gillingwater TH; Jones RA; Loughrey CM; McCarroll CS; Bailey ME; Bird A; Cobb S. 2016. Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes. Hum Mol Genet :. PubMed: 27506980 MGI: J:238655
Schafer DP; Heller CT; Gunner G; Heller M; Gordon C; Hammond T; Wolf Y; Jung S; Stevens B. 2016. Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression. Elife 5:. PubMed: 27458802 MGI: J:235289
Su SH; Kao FC; Huang YB; Liao W. 2015. MeCP2 in the rostral striatum maintains local dopamine content critical for psychomotor control. J Neurosci 35(15):6209-20. PubMed: 25878291 MGI: J:221674
Ure K; Lu H; Wang W; Ito-Ishida A; Wu Z; He LJ; Sztainberg Y; Chen W; Tang J; Zoghbi HY. 2016. Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome. Elife 5:. PubMed: 27328321 MGI: J:234272
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: 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: 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: J:196997

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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

Research Areas By Genotype

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

Genotype: Mecp2tm2Bird related

Mammalian Phenotype Terms by Genotype

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

behavior/neurological phenotype

growth/size/body region phenotype

nervous system phenotype

respiratory system phenotype

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

mortality/aging

behavior/neurological phenotype

respiratory system phenotype

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

behavior/neurological phenotype

nervous system phenotype

respiratory system phenotype

growth/size/body region phenotype

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

mortality/aging

behavior/neurological phenotype

respiratory system phenotype

References

Additional References

Additional - Mecp2tm2Bird related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Mecp2^lox-stop

Mecp2^tm2Bird

Allele Symbol: Mecp2^tm2Bird

Genotype: Mecp2^tm2Bird related

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

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

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

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

Additional - Mecp2^tm2Bird related