Overview

Also Known As:Mecp2*R225X

This strain is currently unavailable due to replenishing of cryopreserved stocks. Interested customers can register interest.

Mecp2*R255X mice contain a mutation in the Mecp2 gene, similar to that found in humans with Rett Syndrome (RTT).

Donating Investigator

N. Carolyn Schanen, Alfred I. duPont Hospital for Children

Genetic overview

Genetic Background	Generation

Mecp2^tm1.1Irsf

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

View Genetics

Research Applications

Neurobiology Research
Mouse/Human Gene Homologs

View All Research Applications

Details

Detailed Description

These Mecp2*R255X mice contain the amino acid mutation R255X in exon 4 of the endogenous methyl CpG binding protein 2 (Mecp2) gene. This mutation introduces a premature stop codon within the transcription repression domain-nuclear localization signal region, analogous to a Mecp2 mutation found in humans with Rett Syndrome (RTT). Female carriers are viable and fertile while male hemizygotes have a reduced life span. RTT is a neurodevelopmental disorder which can be caused by point mutations in the Mecp2 gene. Mecp2 is located on the X-chromosome, and exhibits increased expression in the central nervous system during neuronal maturation. Female carriers of the R255X mutation may develop normally or may exhibit a mild phenotype including some obesity, reduced coordination, and lethargy. This is presumably in part due to inactivation of the X-chromosome and the presence of a compensatory wildtype X-chromosome. Hemizygous males develop a severe neurological phenotype. Specifically, males begin to develop hindlimb clasping and exhibit excessive weight gain by 3 weeks of age, being up to 10g heavier than their littermates. They also display behavior defects such as pauses, abnormal gait, and impaired coordination. These mice may be useful for studying impaired neurodevelopmental maturation associated with human RTT.

Development

A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette downstream of exon 3 of the methyl CpG binding protein 2 (Mecp2) gene. A point mutation was introduced in exon 4, corresponding to human amino acid 255, resulting in a non-sense mutation, R255X, commonly found in humans carrying Rett Syndrome (RTT). This targeting construct was electroporated into 129Sv/Pas-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to females carrying Cre-recombinase on a C57BL/6 background to remove the floxed selection cassette. Female Mecp2*R255X mice, lacking the floxed neo cassette, were then crossed to male B6129SF1/J (Stock No. 101043). Upon arrival at The Jackson Laboratory, mutant mice were bred to B6129SF1/J mice for at least one generation to establish the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

101043 B6129SF1/J

Additional Information

Considerations for Choosing Controls

Genetics

Mecp2^tm1.1Irsf

Allele Symbol: Mecp2^tm1.1Irsf

Allele Name	targeted mutation 1.1, International Rett Syndrome Foundation
Allele Type	Targeted (Null/Knockout, Humanized sequence)
Allele Synonym(s)	Mecp2*R255X
Gene Symbol and Name	Mecp2, methyl CpG binding protein 2
Gene Synonym(s)
Promoter	Mecp2, methyl CpG binding protein 2, mouse, laboratory
Strain of Origin	129S2/SvPas
Chromosome	X
Molecular Note	A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette downstream of exon 3 of the methyl CpG binding protein 2 (Mecp2) gene. A point mutation was introduced in exon 4, corresponding to human amino acid 255, resulting in a non-sense mutation, R255X, commonly found in humans carrying Rett Syndrome (RTT). Cre mediated recombination removed the floxed selection cassette. Western blot analysis indicates absence of full-length protein or the predicted truncation product.

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:

Neurobiology Research
- Behavioral and Learning Defects
- Neurodevelopmental Defects
  - Rett's syndrome
  - Autism
Mouse/Human Gene Homologs
- Rett syndrome

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^tm1.1Irsf/Mecp2⁺
involves: 129S2/SvPas * C57BL/6

behavior/neurological phenotype

impaired coordination
- Normal - however, no difference is seen in the motor coordination task of dowel hang time and mice exhibit normal behaviors in the elevated plus maze
- mice show increased footslips in the parallel rod walking task and impaired ability to learn the accelerating rotating rod walking task at 17 weeks of age

tonic-clonic seizures
- two mice show tonic-clonic seizures followed by death after handling

mortality/aging

premature death
- median survival of 224 days

nervous system phenotype

decreased brain weight

tonic-clonic seizures
- two mice show tonic-clonic seizures followed by death after handling

respiratory system phenotype

increased pulmonary respiratory rate
- 8 month old mice exhibit increased breathing rate when exposed to a hypoxic gas challenge

cardiovascular system phenotype

prolonged QT interval
- 8 month old mice show increased corrected QT interval time

increased heart weight
- increase in heart weight by 8 months

growth/size/body region phenotype

increased heart weight
- increase in heart weight by 8 months

increased liver weight
- increase in liver weight by 8 months of age

increased body weight
- mice become overweight by 10 weeks of age

liver/biliary system phenotype

increased liver weight
- increase in liver weight by 8 months of age

Genotype: Mecp2^tm1.1Irsf/Y
involves: 129S2/SvPas * C57BL/6

respiratory system phenotype

increased pulmonary respiratory rate
- 6-8 week old mice have increased breathing rate at baseline and when exposed to a hypoxic gas challenge

behavior/neurological phenotype

impaired contextual conditioning behavior
- mice exhibit impaired contextual long-term memory at 6 weeks of age

impaired coordination
- mice exhibit increased footslips when walking on an array of parallel bars, decreased ability to remain suspended on a 1/4 inch diameter dowel, and impaired ability to learn the accelerating rotating rod walking task at 6 weeks of age

decreased anxiety-related response
- mice make more entries into, travel greater distances, and spend increased time in the open arm of the elevated plus maze at 6 weeks of age, indicating decreased anxiety

cardiovascular system phenotype

prolonged QT interval
- mice over 8 weeks of age show increased corrected QT interval time

irregular heartbeat
- mice over 8 weeks of age show increased incidence of arrhythmia

growth/size/body region phenotype

decreased body weight
- mice are underweight at weaning but recover to wild-type body weight by 6 weeks of age

mortality/aging

premature death
- median survival of 61 days

nervous system phenotype

decreased brain weight

abnormal excitatory postsynaptic potential
- mice exhibit decreased evoked field excitatory post-synaptic potential (fEPSP) slope in CA1 region of the hippocampus

reduced long term potentiation
- mice exhibit decreased evoked field excitatory post-synaptic potential (fEPSP) slope in CA1 region of the hippocampus, indicating impaired long-term potentiation

Genotype: Mecp2^tm1.1Irsf/Y
involves: 129S/Sv * C57BL/6

behavior/neurological phenotype

abnormal gait

limb grasping
- hind limb clasping

impaired coordination

growth/size/body region phenotype

increased body weight
- up to 10g heavier than controls at 3 weeks of age
- exhibit excessive weight gain

Genotype: Mecp2^tm1.1Irsf/Mecp2⁺
involves: 129S/Sv * C57BL/6

behavior/neurological phenotype

impaired coordination
- in some female mice

lethargy
- in some female mice

growth/size/body region phenotype

increased body weight
- moderate obesity seen in some female mice

References

Additional - Mecp2^tm1.1Irsf related

Technical Support

CONTACT TECHNICAL SUPPORT

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

When maintaining a live colony, heterozygous (carrier) females may be bred to B6129SF1/J mice (Stock No. 101043). Mutation is X-linked. Hemizygous (carrier) males have a reduced life span.
- Additional Breeding and Husbandry Support
Citation
When using the Mecp2*R225X mouse strain in a publication, please cite the originating article(s) and include JAX stock #012602 in your Materials and Methods section.

Strain Interest Registration

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This information helps us manage the colony build and better meet the broad needs of the research community.
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Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Mecp2*R225X

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Mecp2tm1.1Irsf

Allele Symbol: Mecp2tm1.1Irsf

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: Mecp2tm1.1Irsf/Mecp2+involves: 129S2/SvPas * C57BL/6

behavior/neurological phenotype

mortality/aging

nervous system phenotype

respiratory system phenotype

cardiovascular system phenotype

growth/size/body region phenotype

liver/biliary system phenotype

Genotype: Mecp2tm1.1Irsf/Yinvolves: 129S2/SvPas * C57BL/6

respiratory system phenotype

behavior/neurological phenotype

cardiovascular system phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

Genotype: Mecp2tm1.1Irsf/Yinvolves: 129S/Sv * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

Genotype: Mecp2tm1.1Irsf/Mecp2+involves: 129S/Sv * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

References

Additional - Mecp2tm1.1Irsf related

Genotyping Protocols

Breeding Considerations

Citation

Strain Interest Registration

Contact Information

Interest

Terms Of Use

Licensing Information

Mecp2^tm1.1Irsf

Allele Symbol: Mecp2^tm1.1Irsf

Genotype: Mecp2^tm1.1Irsf/Mecp2⁺
involves: 129S2/SvPas * C57BL/6

Genotype: Mecp2^tm1.1Irsf/Y
involves: 129S2/SvPas * C57BL/6

Genotype: Mecp2^tm1.1Irsf/Y
involves: 129S/Sv * C57BL/6

Genotype: Mecp2^tm1.1Irsf/Mecp2⁺
involves: 129S/Sv * C57BL/6

Additional - Mecp2^tm1.1Irsf related