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

View Genetics

Research Applications

Research Tools
Neurobiology Research
Mouse/Human Gene Homologs

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

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

View All References

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^lox
Gene Symbol and Name	Mecp2, methyl CpG binding protein 2
Gene Synonym(s)
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 Phenotype

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
(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

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

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

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

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

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

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

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(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

decreased body weight

abnormal tooth morphology
- frequently exhibit uneven wearing of the teeth

mortality/aging

premature death

reproductive system phenotype

cryptorchism

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

behavior/neurological phenotype

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

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

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

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

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

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

behavior/neurological phenotype

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

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

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

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

decreased startle reflex
- mice show a diminished acoustic startle response

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

mortality/aging

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

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

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

behavior/neurological phenotype

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

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

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

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

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 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

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

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

mammalian phenotype

behavior/neurological phenotype
- Normal - time exhibiting aggressive behavior such as wrestling, tail-rattling, boxing, and mounting is similar to controls
- Normal - mice have a nonsignificant trend to reduced total distance traveled
- Normal - mice show similar grooming times to controls
- 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

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

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

nervous system phenotype

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

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
- 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/Product	Description	Price
	X linked -Heterozygous females and Wild-type males for Mecp2<tm1Bird>

Related Products and Services

Frozen Mouse Embryo	B6;129P2-Mecp2<tm1Bird>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129P2-Mecp2<tm1Bird>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129P2-Mecp2<tm1Bird>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129P2-Mecp2<tm1Bird>/J Frozen Embryo	$3373.50

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

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

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 Phenotype

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

Genotype: Mecp2tm1Bird related

Mammalian Phenotype Terms by Genotype

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

behavior/neurological phenotype

mortality/aging

nervous system 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(129S6.129P2-Mecp2 x C57BL/6)F1

mammalian phenotype

nervous system phenotype

behavior/neurological phenotype

growth/size/body region phenotype

integument phenotype

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

behavior/neurological phenotype

mammalian phenotype

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

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

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

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

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

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

Additional - Mecp2^tm1Bird related