Overview

Also Known As:MeCP2 T158A

The amino acid mutation T158A was introduced into exon 4 of the mouse methyl-CpG binding protein 2 (Mecp2) gene, resulting in a phenotypic pattern similar to that observed in patients with Rett Syndrome.

Due to demand, this colony is being expanded. An estimated distribution date is provided above.

Donating Investigator

Zhaolan (Joe) Zhou, University of Pennsylvania

Genetic overview

Genetic Background	Generation

Mecp2^tm1.1Joez

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Mecp2	methyl CpG binding protein 2

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Research Applications

Mouse/Human Gene Homologs
Neurobiology Research
Reproductive Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Important Note

Due to demand, this colony is being expanded. An estimated distribution date is provided above.

Detailed Description

These Mecp2^T158A mice contain a missense mutation in exon 4 of the endogenous methyl-CpG binding protein 2 (Mecp2) gene. This mutation introduces the amino acid mutation T158A in the methyl CpG binding domain (MBD) of MeCP2, analogous to a MECP2 mutation found in humans with Rett Syndrome (RTT). RTT is an X-linked neurodevelopmental disorder that can be caused by mutations in the Mecp2 gene. Hemizygous males with the T158A mutation exhibit hypoactivity, poor motor control, irregular breathing, altered anxiety, and impaired learning and memory after 5-6 weeks of age. They are infertile and have a shortened lifespan, with 50% of males dying by 4 months of age. Symptoms in heterozygous females are obvious after 17 weeks of age. Heterozygous females are viable and fertile. The differences seen between the sexes is because Mecp2 is an X-linked gene. Due to X-chromosome inactivation, heterozygous females have mosaic expression of wild-type MeCP2.

Development

A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette upstream of exon 4 of the methyl-CpG binding protein 2 (Mecp2) gene. This mutation introduces the amino acid mutation T158A found in humans carrying the neurodevelopmental disorder Rett Syndrome (RTT). This targeting construct was electroporated into 129Sv derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric males were bred to C57BL/6 females and offspring were bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J transgenic mice (Stock No. 003724) to remove the neo cassette. The resulting offspring were backcrossed to C57BL/6NCrL for at least 10 generations. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6NJ mice (Stock No. 005304) for at least one generation to establish the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Goffin D; Allen M; Zhang L; Amorim M; Wang IT; Reyes AR; Mercado-Berton A; Ong C; Cohen S; Hu L; Blendy JA; Carlson GC; Siegel SJ; Greenberg ME; Zhou Z. 2012. Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Nat Neurosci 15(2):274-83PubMed: 22119903 MGI: J:181311

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Genetics

Mecp2^tm1.1Joez

Allele Symbol: Mecp2^tm1.1Joez

Allele Name	targeted mutation 1.1, Zhaolan Zhou
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	targeted mutation 1.1, Zhaolan Zhou; Mecp2^tm1.1Joez
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
Promoter	Mecp2, methyl CpG binding protein 2, mouse, laboratory
Strain of Origin	129
Chromosome	X
Molecular Note	A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette upstream of exon 4. A point mutation was introduced in exon 4, resulting in the amino acid mutation, T158A, found in humans carrying the neurodevelopmental disorder Rett Syndrome (RTT). An additional point mutation was introduced at codon 160 to produce a silent mutation that allowed for identification of targeted ES cells. Cre-mediated recombination removed the neo cassette.
Mutations Made By	Zhaolan (Joe) Zhou, University of Pennsylvania

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:

Mouse/Human Gene Homologs
- Rett syndrome
Neurobiology Research
- Neurodevelopmental Defects
  - Rett's syndrome
- Behavioral and Learning Defects
  - high anxiety
Reproductive Biology Research
- Fertility Defects
  - males only

Mammalian Phenotype Terms by Genotype

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

Genotype: Mecp2^tm1.1Joez/Y
B6.129-Mecp2

behavior/neurological phenotype

abnormal behavior
- mice exhibit RTT-like symptoms after 5 weeks of age

abnormal gait
- with splaying hind limbs upon movement

abnormal motor learning
- impaired motor learning on a rotarod

akinesia

decreased anxiety-related response
- in an elevated zero maze

hypoactivity
- at 11, but not 3, weeks of age
- not as severe as in Mecp2^tm1.1Jae hemizygotes

impaired contextual conditioning behavior

impaired coordination
- not as severe as in Mecp2^tm1.1Jae hemizygotes
- on a rotarod

impaired cued conditioning behavior

limb grasping
- at 13 weeks of age

seizures
- occasionally after 5 weeks of age

growth/size/body region phenotype

decreased body weight
- between 4 and 8 weeks of age

mortality/aging

premature death
- 50% of mice die by 16 weeks of age

nervous system phenotype

abnormal brain wave pattern
- at P30, mice exhibit less of an increase in phase-locking factor at delta and high gamma frequencies compared with wild-type mice
- at P30, mice exhibit reduction in event-related power in delta, sigma and alpha low-frequencies compared with wild-type mice
- at P90, awake mice exhibit increased high-gamma frequency oscillation power compared with wild-type mice
- at P90, mice exhibit an increase in latency of P1, N1 and P2 peaks and reduction in the amplitudes of the N1 and P2 peaks of event-related potential compared with wild-type mice
- at P90, mice exhibit attenuated event-related power in both low- and high-frequency oscillation compared with wild-type mice
- at P90, mice exhibit less of an increase in phase-locking factor at all frequencies compared with wild-type mice
- Normal - however, mice exhibit normal power and event-related potential at P30

decreased brain weight
- at P30 and P90

seizures
- occasionally after 5 weeks of age

Genotype: Mecp2^tm1.1Joez/Mecp2⁺
B6.129-Mecp2

behavior/neurological phenotype

abnormal behavior
- mice exhibit RTT-like symptoms after 17 weeks of age

hypoactivity
- at 20, but not 12, weeks of age

growth/size/body region phenotype

increased body weight

mammalian phenotype

mortality/aging
- Normal - mice exhibit normal survival

References

Goffin D; Allen M; Zhang L; Amorim M; Wang IT; Reyes AR; Mercado-Berton A; Ong C; Cohen S; Hu L; Blendy JA; Carlson GC; Siegel SJ; Greenberg ME; Zhou Z. 2012. Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Nat Neurosci 15(2):274-83PubMed: 22119903 MGI: J:181311

Additional - Mecp2^tm1.1Joez related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Mecp2
- Standard PCR:Generic Cre Melt Curve Analysis
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous females may be bred to wildtype males. Hemizygous males are infertile and have a shortened lifespan, with 50% of males dying by 4 months of age.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Wild-type
Citation
When using the MeCP2 T158A mouse strain in a publication, please cite the originating article(s) and include JAX stock #017741 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
	Females are Heterozygous or wild-type and males are Hemizygous or Non Carrier for Mecp2<tm1.1Joez>

Related Products and Services

Frozen Mouse Embryo	B6N.129(Cg)-Mecp2<tm1.1Joez>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6N.129(Cg)-Mecp2<tm1.1Joez>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6N.129(Cg)-Mecp2<tm1.1Joez>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6N.129(Cg)-Mecp2<tm1.1Joez>/J Frozen Embryos	$3373.50

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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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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As:MeCP2 T158A

Donating Investigator

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Mecp2tm1.1Joez

Allele Symbol: Mecp2tm1.1Joez

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:

Mammalian Phenotype Terms by Genotype

Genotype: Mecp2tm1.1Joez/YB6.129-Mecp2

behavior/neurological phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

Genotype: Mecp2tm1.1Joez/Mecp2+B6.129-Mecp2

behavior/neurological phenotype

growth/size/body region phenotype

mammalian phenotype

References

Additional - Mecp2tm1.1Joez related

Genotyping Protocols

Breeding Considerations

Mating System

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

Additional Use Restrictions Apply

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^tm1.1Joez

Allele Symbol: Mecp2^tm1.1Joez

Genotype: Mecp2^tm1.1Joez/Y
B6.129-Mecp2

Genotype: Mecp2^tm1.1Joez/Mecp2⁺
B6.129-Mecp2

Additional - Mecp2^tm1.1Joez related