Overview

These floxed mutant mice possess loxP sites flanking exons 3-4 of the Mecp2 gene. This strain may be useful for generating conditional mutations in applications related to neurological and developmental studies of Rett syndrome.

Donating Investigator

Adrian Bird, University of Edinburgh

Genetic overview

Genetic Background	Generation

Mecp2^tm1Bird

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	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 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 Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

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):322-6PubMed: 11242117 MGI: J:67910

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Genetics

Mecp2^tm1Bird

Allele Symbol: Mecp2^tm1Bird

Allele Name	targeted mutation 1, Adrian Bird
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Mecp2^tm1Bird; targeted mutation 1, Adrian Bird
Gene Symbol and Name	Mecp2, methyl CpG binding protein 2
Gene Synonym(s)	AUTSX3; RTS; RIKEN cDNA 1500041B07 gene; D630021H01Rik; PPMX; D630021H01Rik; expressed sequence BB130002; WBP10; RIKEN cDNA D630021H01 gene; Mbd5; MRX16; MRX79; MRXS13; RS; RTT; MRXSL; 1500041B07Rik; BB130002; 1500041B07Rik
Strain of Origin	129P2/OlaHsd
Chromosome	X
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.
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 Genotype

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

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

Genotype: Mecp2^tm1Bird 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^tm1Bird/Y Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * SJL

behavior/neurological phenotype

abnormal gait
- develop a stiff, uncoordinated gait

hypoactivity

limb grasping

skeleton phenotype

abnormal tooth morphology
- frequently exhibit uneven wearing of the teeth

craniofacial phenotype

abnormal tooth morphology
- frequently exhibit uneven wearing of the teeth

endocrine/exocrine gland phenotype

cryptorchism

growth/size/body region phenotype

abnormal tooth morphology
- frequently exhibit uneven wearing of the teeth

decreased body weight

mortality/aging

premature death

reproductive system phenotype

cryptorchism

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

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

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

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

decreased startle reflex
- mice have a decreased startle response relative to wild-type

impaired coordination
- Background Sensitivity - mice display impaired performance in coordination tasks like the rotating rod, hanging wire, and dowel walking tests

increased thermal nociceptive threshold
- mice show increased latency in the hot plate assay

mammalian phenotype

mortality/aging
- Normal - no early mortality is observed in contrast to Mecp2-null animals

nervous system phenotype

decreased prepulse inhibition
- mice show decreased prepulse inhibition at 74 and 82 decibels compared to wild-type

growth/size/body region phenotype

increased body weight
- Background Sensitivity - a mild increase (animals are about 1 gram heavier) is observed relative to wild-type or F1 mutants from an FVB/N cross

integument phenotype

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

increased thermal nociceptive threshold
- mice show increased latency in the hot plate assay

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

behavior/neurological phenotype

abnormal contextual conditioning behavior
- percentage of time spent freezing is elevated relative to wild-type when placed back into the conditioning chamber

abnormal cued conditioning behavior
- percentage of time spent freezing is elevated relative to wild-type when re-exposure to a previously experienced cue

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

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

decreased anxiety-related response
- mice show decrease anxiety-related behavior in open field assays than wild-type mice

increased vertical activity
- increased number of vertical explorations is observed compared to wild-type; this is indicative of reduced anxiety

nervous system phenotype

decreased prepulse inhibition
- mice show decreased prepulse inhibition compared to wild-type

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

apnea
- increase in apnea incidence (39.5/hour) is observed compared to wild-type (5.8/hour)

integument phenotype

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

mammalian phenotype

behavior/neurological phenotype
- Normal - mice do not show overt abnormalities like tremor or limb grasping
- Background Sensitivity - no overt abnormalities are observed; mutants do not exhibit impaired coordination in a variety of tests measured

growth/size/body region phenotype
- Background Sensitivity - no size difference is detected relative to wild-type, unlike mice on the C57BL/6 background

mortality/aging
- Normal - no early mortality is observed in contrast to Mecp2-null animals

Genotype: Mecp2^tm1Bird/Y Tg(dlx5a-cre)1Mekk/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N

behavior/neurological phenotype

abnormal nest building behavior
- nest building is impaired

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

decreased startle reflex
- mice show impaired maximum acoustic startle response to 120dB

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

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

nervous system phenotype

increased prepulse inhibition
- 24 week-old mice show increased prepulse inhibition at 74 dB

mammalian phenotype

behavior/neurological phenotype
- Normal - at 12 weeks, mice have intact nociception demonstrated by a hot-plate or tail-flick assay
- Normal - mice exhibit intact olfactory recognition and habituation in response to a novel odorant at 11 weeks of age
- Normal - mice have a nonsignificant trend to reduced total distance traveled
- Normal - mice show similar grooming times to controls
- Normal - time exhibiting aggressive behavior such as wrestling, tail-rattling, boxing, and mounting is similar to controls

mortality/aging
- Normal - mice survive to at least 80 weeks of age

respiratory system phenotype
- Normal - mice show no alterations in tidal volume or minute volume, and display no apneas

Genotype: Mecp2^tm1Bird/Y Pvalb^{tm1.1(cre)Aibs}/Pvalb⁺
involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

behavior/neurological phenotype

abnormal gait
- mice develop widely splayed hind limbs after 10 weeks and hind limb retraction after 15 weeks of age

abnormal social investigation
- mice spend more time interacting with novel partner mice in a social behavior assay

ataxia
- Normal - however, mice do not exhibit seizures or stereotypical behaviors
- mice develop progressive ataxia that is apparent at 6 weeks and worsens by 20 weeks

decreased startle reflex
- mice show a diminished acoustic startle response

impaired coordination
- mice exhibit impaired performance of the marble-burying test, suggesting forelimb incoordination
- mice exhibit reduced latency to fall in both the rotarod and dowel walk assays

impaired cued conditioning behavior
- mice develop progressive cued memory deficits, with the difference in freezing response to a conditioned tone becoming significantly different at 15 weeks of age

mortality/aging

premature death
- 50% mortality by 29-35 weeks of age

Genotype: Mecp2^tm1Bird/Y Sst^{tm2.1(cre)Zjh}/Sst⁺
involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

behavior/neurological phenotype

increased stereotypic behavior
- Normal - however, mice do not exhibit motor deficits or alternations in acoustic startle response, partition, or cued memory tests, or differences in anxiety, pre-pulse inhibition, locomotor activity or long-term potentiation
- mice exhibit repetitive nose-poking behavior in the hole board test

seizures
- 50% of mice develop spontaneous epileptic seizures starting at 12 weeks

tonic-clonic seizures
- mice show generalized tonic clonic seizures during routine handling

mortality/aging

premature death
- 50% mortality by 29-35 weeks of age

nervous system phenotype

seizures
- 50% of mice develop spontaneous epileptic seizures starting at 12 weeks

tonic-clonic seizures
- mice show generalized tonic clonic seizures during routine handling

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

Genotype: Mecp2^tm1Bird/Y
involves: 129P2/OlaHsd * C57BL/6J * FVB/N

mammalian phenotype

mortality/aging
- Normal - mice do not show premature lethality

respiratory system phenotype
- Normal - mice do not exhibit apneas

References

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):322-6PubMed: 11242117 MGI: J:67910

Additional - Mecp2^tm1Bird related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Mecp2^tm1Bird
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, females homozygous for this X-linked mutation can be bred with males hemizygous for this X-linked mutation.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129P2-Mecp2^tm1Bird/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006847 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	Genotype	Price
	X linked -Heterozygous females and Wild-type males for Mecp2<tm1Bird>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Mecp2tm1Bird

Allele Symbol: Mecp2tm1Bird

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 Genotype

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

Genotype: Mecp2tm1Bird related

Mammalian Phenotype Terms by Genotype

Genotype: Mecp2tm1Bird/Y Tg(Nes-cre)1Kln/0involves: 129P2/OlaHsd * C57BL/6 * SJL

behavior/neurological phenotype

skeleton phenotype

craniofacial phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

mortality/aging

reproductive system phenotype

Genotype: Mecp2tm1Bird/Y(129S6.129P2-Mecp2 x C57BL/6)F1

behavior/neurological phenotype

mammalian phenotype

nervous system phenotype

growth/size/body region phenotype

integument phenotype

Genotype: Mecp2tm1Bird/Y(129S6.129P2-Mecp2 x FVB/N)F1

behavior/neurological phenotype

nervous system phenotype

respiratory system phenotype

integument phenotype

mammalian phenotype

Genotype: Mecp2tm1Bird/Y Tg(dlx5a-cre)1Mekk/0involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N

behavior/neurological phenotype

nervous system phenotype

mammalian phenotype

Genotype: Mecp2tm1Bird/Y Pvalbtm1.1(cre)Aibs/Pvalb+involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

behavior/neurological phenotype

mortality/aging

Genotype: Mecp2tm1Bird/Y Ssttm2.1(cre)Zjh/Sst+involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

behavior/neurological phenotype

mortality/aging

nervous system phenotype

Genotype: Mecp2tm1Bird/Yinvolves: 129P2/OlaHsd * C57BL/6J * FVB/N

mammalian phenotype

References

Additional - Mecp2tm1Bird 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

Related Products and Services

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

Mecp2^tm1Bird

Allele Symbol: Mecp2^tm1Bird

Genotype: Mecp2^tm1Bird related

Genotype: Mecp2^tm1Bird/Y Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * SJL

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

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

Genotype: Mecp2^tm1Bird/Y Tg(dlx5a-cre)1Mekk/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N

Genotype: Mecp2^tm1Bird/Y Pvalb^{tm1.1(cre)Aibs}/Pvalb⁺
involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

Genotype: Mecp2^tm1Bird/Y Sst^{tm2.1(cre)Zjh}/Sst⁺
involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

Genotype: Mecp2^tm1Bird/Y
involves: 129P2/OlaHsd * C57BL/6J * FVB/N

Additional - Mecp2^tm1Bird related