Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x +/+ sibling         (Female x Male)   08-JUL-10 Species laboratory mouse Generation N?+N1F8 (23-MAY-13) Generation Definitions   Donating Investigator Adrian Bird,   University of Edinburgh

Description
These mice possess two functional loxP sites flanking exons 3-4 of the targeted gene on the X chromosome. Homozygous females and hemizygous males are viable and fertile. Northern blot analysis showed the expected mature transcript from the Mecp2^lox locus. Also detected was an unspliced beta-globin transcript that was introduced into the locus as part of the targeting vector. When these mutant mice are bred to mice that express cre recombinase, resulting offspring will have exons 3-4 deleted in the cre-expressing tissue(s). Mice with this X-linked floxed mutation may be useful in neurological and developmental studies of Rett syndrome.

For example, when crossed to a strain expressing Cre recombinase in nervous tissue (see Stock No. 003771), this mutant mouse strain develops a neurological phenotype that mimics Rett syndrome.

When bred to a strain expressing Cre recombinase in embryonic forebrain GABAergic neurons (see Stock No. 008199 for example), this mutant mouse strain may be useful in studies of diseases related to GABA (gamma-aminobutyric acid)-releasing neurons.

When crossed to a strain expressing Cre recombinase in GABAergic neurons (see Stock No. 017535), these mice exhibit behaviors common to those seen in Rett Syndrome and Autism Spectrum Disorders.

Development
A targeting vector was designed to insert a loxP site upstream of exon 3, as well as a human beta-globin intron 2 and polyadenylation signal followed by a loxp-flanked TK-neo cassette all downstream of the stop codon in exon 4, of the targeted gene. The donating investigator reports that the "middle" loxP site (just 5' of the TK-neo cassette) is non-functional; thus only the loxP sites upstream of exon 3 and downstream of the TK-neo cassette are functional. 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 females (with exons 3-4 flanked by functional loxP sites) were mated with wild-type C57BL/6 animals. The resulting hemizygous males were bred with heterozygous females to generate homozygous females. Homozygous females and hemizygous males were bred together for many generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	100492 B6129PF1/J	(approximate)
	100903 B6129PF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Mecp2^tm1Bird allele

007177

B6.129P2-Mecp2tm1Bird/J

View Strains carrying   Mecp2^tm1Bird     (1 strain)

Strains carrying other alleles of Mecp2

003890	B6.129P2(C)-Mecp2tm1.1Bird/J
006849	B6.129P2-Mecp2tm2Bird/J
005439	B6.129S-Mecp2tm1Hzo/J
018282	B6.Cg-Mapttm1(Mecp2)Jae/LimmJ
017741	B6N.129(Cg)-Mecp2tm1.1Joez/J
016207	B6N.129-Mecp2tm1.1Vnar/J
012602	STOCK Mecp2tm1.1Irsf/J
014610	STOCK Mecp2tm3.1Bird/J

View Strains carrying other alleles of Mecp2     (8 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

Mecp2^tm1Bird/Y

        involves: 129P2/OlaHsd * C57BL/6J * FVB/N

• mortality/aging
• *normal* mortality/aging
  • mice do not show premature lethality   (MGI Ref ID J:166851)
• respiratory system phenotype
• *normal* respiratory system phenotype
  • mice do not exhibit apneas   (MGI Ref ID J:166851)

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

Mecp2^tm1Bird/Y

        (129S6.129P2-Mecp2^tm1Bird x C57BL/6)F1

• mortality/aging
• *normal* mortality/aging
  • no early mortality is observed in contrast to Mecp2-null animals   (MGI Ref ID J:135825)
• growth/size phenotype
• increased body weight
  • a mild increase (animals are about 1 gram heavier) is observed relative to wild-type or F1 mutants from an FVB/N cross   (MGI Ref ID J:135825)
• behavior/neurological phenotype
• abnormal nest building behavior
  • mice show deficits in nest-building relative to wild-type, with fewer animals building or completing nests than wild-type animals over the same time period   (MGI Ref ID J:135825)
• abnormal social investigation
  • mice have altered social behavior and spend more time than wild-type animals interacting with an unfamiliar mouse or with a 'familiar' mouse that has been reintroduced into the cage   (MGI Ref ID J:135825)
• abnormal touch/ nociception
  • mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity   (MGI Ref ID J:135825)
• • increased thermal nociceptive threshold
    • mice show increased latency in the hot plate assay   (MGI Ref ID J:135825)
• decreased startle reflex
  • mice have a decreased startle response relative to wild-type   (MGI Ref ID J:135825)
• impaired coordination
  • mice display impaired performance in coordination tasks like the rotating rod, hanging wire, and dowel walking tests   (MGI Ref ID J:135825)
• nervous system phenotype
• decreased prepulse inhibition
  • mice show decreased prepulse inhibition at 74 and 82 decibels compared to wild-type   (MGI Ref ID J:135825)
• integument phenotype
• abnormal touch/ nociception
  • mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity   (MGI Ref ID J:135825)
• • increased thermal nociceptive threshold
    • mice show increased latency in the hot plate assay   (MGI Ref ID J:135825)

Mecp2^tm1Bird/Y

        (129S6.129P2-Mecp2^tm1Bird x FVB/N)F1

• mortality/aging
• *normal* mortality/aging
  • no early mortality is observed in contrast to Mecp2-null animals   (MGI Ref ID J:135825)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • no overt abnormalities are observed; mutants do not exhibit impaired coordination in a variety of tests measured   (MGI Ref ID J:135825)
  • mice do not show overt abnormalities like tremor or limb grasping   (MGI Ref ID J:135825)
• • abnormal contextual conditioning behavior
    • percentage of time spent freezing is elevated relative to wild-type when placed back into the conditioning chamber   (MGI Ref ID J:135825)
  • abnormal cued conditioning behavior
    • percentage of time spent freezing is elevated relative to wild-type when re-exposure to a previously experienced cue   (MGI Ref ID J:135825)
  • abnormal social investigation
    • mice have altered social behavior and spend more time than wild-type animals interacting with an unfamiliar mouse or with a 'familiar' mouse that has been reintroduced into the cage   (MGI Ref ID J:135825)
  • abnormal touch/ nociception
    • mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity   (MGI Ref ID J:135825)
  • decreased anxiety-related response
    • mice show decrease anxiety-related behavior in open field assays than wild-type mice   (MGI Ref ID J:135825)
  • increased vertical activity
    • increased number of vertical explorations is observed compared to wild-type; this is indicative of reduced anxiety   (MGI Ref ID J:135825)
• nervous system phenotype
• decreased prepulse inhibition
  • mice show decreased prepulse inhibition compared to wild-type   (MGI Ref ID J:135825)
• respiratory system phenotype
• abnormal breathing pattern
  • at 4 months, respiratory pattern is qualitatively different than in wild-type; coefficient of variability of the respiratory rhythm is higher than in wild-type   (MGI Ref ID J:135825)
• • apnea
    • increase in apnea incidence (39.5/hour) is observed compared to wild-type (5.8/hour)   (MGI Ref ID J:135825)
• growth/size phenotype
• *normal* growth/size phenotype
  • no size difference is detected relative to wild-type, unlike mice on the C57BL/6 background   (MGI Ref ID J:135825)
• integument phenotype
• abnormal touch/ nociception
  • mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity   (MGI Ref ID J:135825)

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

Mecp2^tm1Bird/Y Tg(Nes-cre)1Kln/0

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

• mortality/aging
• premature death   (MGI Ref ID J:67910)
• behavior/neurological phenotype
• abnormal gait
  • develop a stiff, uncoordinated gait   (MGI Ref ID J:67910)
• hypoactivity   (MGI Ref ID J:67910)
• limb grasping   (MGI Ref ID J:67910)
• craniofacial phenotype
• abnormal tooth morphology
  • frequently exhibit uneven wearing of the teeth   (MGI Ref ID J:67910)
• endocrine/exocrine gland phenotype
• cryptorchism   (MGI Ref ID J:67910)
• growth/size phenotype
• decreased body weight   (MGI Ref ID J:67910)
• reproductive system phenotype
• cryptorchism   (MGI Ref ID J:67910)

Mecp2^tm1Bird/Y Tg(dlx6a-cre)1Mekk/0

        involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB   (conditional)

• mortality/aging
• *normal* mortality/aging
  • mice survive to at least 80 weeks of age   (MGI Ref ID J:166851)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • mice show similar grooming times to controls   (MGI Ref ID J:166851)
  • mice have a nonsignificant trend to reduced total distance traveled   (MGI Ref ID J:166851)
  • time exhibiting aggressive behavior such as wrestling, tail-rattling, boxing, and mounting is similar to controls   (MGI Ref ID J:166851)
  • mice exhibit intact olfactory recognition and habituation in response to a novel odorant at 11 weeks of age   (MGI Ref ID J:166851)
  • at 12 weeks, mice have intact nociception demonstrated by a hot-plate or tail-flick assay   (MGI Ref ID J:166851)
• • abnormal nest building behavior
    • nest building is impaired   (MGI Ref ID J:166851)
  • abnormal social investigation
    • mice show increased social interaction with novel and familiar partners; time spent with novel partners is 60% higher than in controls in a 3-chamber assay   (MGI Ref ID J:166851)
  • decreased startle reflex
    • mice show impaired maximum acoustic startle response to 120dB   (MGI Ref ID J:166851)
  • impaired coordination
    • mice display more footslips, shorter latency to fall on wire, reduced number of side touches on dowel and shorter latency to fall from rotarod compared to controls   (MGI Ref ID J:166851)
  • increased stereotypic behavior
    • mice show a 200% increase relative to control in number of holes explored with 2 or more sequential nose pokes in a holeboard assay   (MGI Ref ID J:166851)
• nervous system phenotype
• increased prepulse inhibition
  • 24 week-old mice show increased prepulse inhibition at 74 dB   (MGI Ref ID J:166851)
• respiratory system phenotype
• *normal* respiratory system phenotype
  • mice show no alterations in tidal volume or minute volume, and display no apneas   (MGI Ref ID J:166851)

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

Mecp2^tm1Bird related

Neurobiology Research
Ataxia (Movement) Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mecp2tm1Bird
Allele Name		targeted mutation 1, Adrian Bird
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Mecp2lox;
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; MRX16; MRX79; MRXS13; MRXSL; Mbd5; PPMX; RIKEN cDNA 1500041B07 gene; RIKEN cDNA D630021H01 gene; RS; RTS; RTT; WBP10; expressed sequence BB130002;
Molecular Note		Insertion of a neomycin resistance cassette into the gene introduced loxP sites that flank exons 3 and 4, and added an intron and polyadenylation signal from the human beta globin gene. From the mutated allele, Northern blot analysis detected the wild type mature transcript and also a transcript in which the beta globin intron was unspliced. [MGI Ref ID J:67910]

Genotyping

Genotyping Information

Genotyping Protocols

Mecp2^tm1Bird, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Guy J; Hendrich B; Holmes M; Martin JE; Bird A. 2001. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27(3):322-6. [PubMed: 11242117]  [MGI Ref ID J:67910]

Additional References

Mecp2^tm1Bird related

Chao HT; Chen H; Samaco RC; Xue M; Chahrour M; Yoo J; Neul JL; Gong S; Lu HC; Heintz N; Ekker M; Rubenstein JL; Noebels JL; Rosenmund C; Zoghbi HY. 2010. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468(7321):263-9. [PubMed: 21068835]  [MGI Ref ID J:166851]

Cheval H; Guy J; Merusi C; De Sousa D; Selfridge J; Bird A. 2012. Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows. Hum Mol Genet 21(17):3806-14. [PubMed: 22653753]  [MGI Ref ID J:185982]

Fyffe SL; Neul JL; Samaco RC; Chao HT; Ben-Shachar S; Moretti P; McGill BE; Goulding EH; Sullivan E; Tecott LH; Zoghbi HY. 2008. Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, aggression, and the response to stress. Neuron 59(6):947-58. [PubMed: 18817733]  [MGI Ref ID J:143360]

Maliszewska-Cyna E; Bawa D; Eubanks JH. 2010. Diminished prevalence but preserved synaptic distribution of N-methyl-d-aspartate receptor subunits in the methyl CpG binding protein 2(MeCP2)-null mouse brain. Neuroscience 168(3):624-32. [PubMed: 20381590]  [MGI Ref ID J:161478]

McCauley MD; Wang T; Mike E; Herrera J; Beavers DL; Huang TW; Ward CS; Skinner S; Percy AK; Glaze DG; Wehrens XH; Neul JL. 2011. Pathogenesis of lethal cardiac arrhythmias in Mecp2 mutant mice: implication for therapy in Rett syndrome. Sci Transl Med 3(113):113ra125. [PubMed: 22174313]  [MGI Ref ID J:183640]

McGraw CM; Samaco RC; Zoghbi HY. 2011. Adult neural function requires MeCP2. Science 333(6039):186. [PubMed: 21636743]  [MGI Ref ID J:173307]

Nguyen MV; Du F; Felice CA; Shan X; Nigam A; Mandel G; Robinson JK; Ballas N. 2012. MeCP2 Is Critical for Maintaining Mature Neuronal Networks and Global Brain Anatomy during Late Stages of Postnatal Brain Development and in the Mature Adult Brain. J Neurosci 32(29):10021-34. [PubMed: 22815516]  [MGI Ref ID J:186548]

Peddada S; Yasui DH; LaSalle JM. 2006. Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome. Hum Mol Genet 15(12):2003-14. [PubMed: 16682435]  [MGI Ref ID J:112064]

Samaco RC; Fryer JD; Ren J; Fyffe S; Chao HT; Sun Y; Greer JJ; Zoghbi HY; Neul JL. 2008. A partial loss of function allele of methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome. Hum Mol Genet 17(12):1718-27. [PubMed: 18321864]  [MGI Ref ID J:135825]

Samaco RC; Mandel-Brehm C; Chao HT; Ward CS; Fyffe-Maricich SL; Ren J; Hyland K; Thaller C; Maricich SM; Humphreys P; Greer JJ; Percy A; Glaze DG; Zoghbi HY; Neul JL. 2009. Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities. Proc Natl Acad Sci U S A :. [PubMed: 20007372]  [MGI Ref ID J:155808]

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]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, females homozygous for this X-linked mutation can be bred with males hemizygous for this X-linked mutation.
Mating System	Heterozygote x +/+ sibling         (Female x Male)   08-JUL-10
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	100492 B6129PF1/J	(approximate)
	100903 B6129PF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

See Terms of Use tab for General Terms and Conditions

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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Ordering Information
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