Overview

Also Known As:Mecp2^R168X knock-in mice

This strain is currently unavailable due to replenishing of cryopreserved stocks. Interested customers who register interest will be contacted when the strain is again available.

Mecp2^R168X knock-in mice develop impaired motor function, and behavioral abnormalities such as reduced anxiety. This strain may be useful for in studies of Rett syndrome.

Donating Investigator

Peter Huppke, University Medical Center Gottingen

Genetic overview

Genetic Background	Generation

Mecp2^tm1.1Hupp

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

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Research Applications

Neurobiology Research
Research Tools

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Details

Detailed Description

The nonsense R168X mutation is one of the most common MeCP2 mutations associated with Rett syndrome (RTT), and produces a truncated mutant protein. These mice carry the R168X knock-in mutation of the Mecp2. An in-frame UGA stop codon is introduced with the adenine at position 502 substituted with thymine in exon 4.
While gene transcript is detected by RT-PCR in total RNA from brain tissue of mutant male mice, no full length or truncated protein is detected in nuclear extracts from brain tissue of hemizygous males. Sequencing confirmed the presence of the mutation.
Hemizygous males are smaller than wildtype littermates and exhibit tremors, hind limb clasping, hypoactivity, irregular breathing, and apnea as early as 27 days of age. Impaired motor performance and decreased anxiety-like behavior of hemizygous males are observed by 6 weeks of age.
Heterozygous females start to develop tremor and hind limb clasping as early as 36 days. By 9 months of age, female heterozygotes exhibit impaired motor control. Mutant mice have poor nest building abilities. Hemizygous males have a median lifespan of 57 days of age, and lifespan range of 23 to 150 days.

Development

A targeting vector containing a FRT site flanked NEO cassette was used to insert the R168X point mutation (502 A to T) into exon 4. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to C57BL/6 females. Heterozygous female mice were were bred to 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J (Stock No. 003946) male mice to remove the FRT site flanked NEO cassette. The mice were then backcrossed to C57BL/6JRj (JANVIER LABS) for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J inbred mice (Stock No. 000664) at least once to establish the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Brendel C; Belakhov V; Werner H; Wegener E; Gartner J; Nudelman I; Baasov T; Huppke P. 2011. Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model. J Mol Med (Berl) 89(4):389-98PubMed: 21120444 MGI: J:285039

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Genetics

Mecp2^tm1.1Hupp

Allele Symbol: Mecp2^tm1.1Hupp

Allele Name	targeted mutation 1.1, Peter Huppke
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	Mexp2^R168X
Gene Symbol and Name	Mecp2, methyl CpG binding protein 2
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	X
Molecular Note	A targeting vector containing an FRT flanked neomycin cassette was used to insert an in-frame UGA stop codon in place of the codon (AGA) for arginine (R168X) at position 502 in exon 4. R168X is the most common nonsense mutation associated with Rhett syndrome. Flp-mediated recombination removed the FRT-flanked neo cassette.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Ataxia (Movement) Defects
- Neurodevelopmental Defects
  - Rett's syndrome
- Tremor Defects
- Behavioral and Learning Defects
Research Tools
- Neurobiology Research

Mammalian Phenotype Terms by Genotype

References

Brendel C; Belakhov V; Werner H; Wegener E; Gartner J; Nudelman I; Baasov T; Huppke P. 2011. Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model. J Mol Med (Berl) 89(4):389-98PubMed: 21120444 MGI: J:285039

Additional - Mecp2^tm1.1Hupp related

Technical Support

CONTACT TECHNICAL SUPPORT

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

When maintaining a live colony, heterozygous females may be bred with wildtype males from the colony. Median life span for hemizygous males is 57 days of age.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Wild-type
Citation
When using the Mecp2^R168X knock-in mice mouse strain in a publication, please cite the originating article(s) and include JAX stock #019528 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.
Please send any technical questions to Technical Support.

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Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Mecp2R168X knock-in mice

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Mecp2tm1.1Hupp

Allele Symbol: Mecp2tm1.1Hupp

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Mecp2tm1.1Hupp related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Strain Interest Registration

Contact Information

Interest

Terms Of Use

Licensing Information

Also Known As:Mecp2^R168X knock-in mice

Mecp2^tm1.1Hupp

Allele Symbol: Mecp2^tm1.1Hupp

Additional - Mecp2^tm1.1Hupp related