Overview

Also Known As:Mecp2³⁰⁸

Mecp2³⁰⁸ mice have a loxP-flanked neomycin resistance and herpes simplex virus thymidine kinase genes that disrupt exon 4, with a stop codon inserted after Mecp2 codon 308. By 6 weeks of age, male mutant mice of this strain begin to exhibit tremors, progressive motor dysfunction, oily disheveled fur, hypoactivity, myoclonic seizures, and kyphosis. This mutant mouse strain may be useful in studies of Rett Syndrome.

Donating Investigator

Huda Zoghbi, Baylor College of Medicine

Genetic overview

Genetic Background	Generation

Mecp2^tm1Hzo

Allele Type	Gene Symbol	Gene Name
Targeted (Not Applicable)	Mecp2	methyl CpG binding protein 2

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Research Applications

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

Mice that are homozygous for the targeted mutation are viable and fertile. A truncated gene product (protein) is detected by immunohistochemical analysis of brain tissue. By 6 weeks of age, male mutant mice begin to exhibit tremors, progressive motor dysfunction, oily disheveled fur, hypoactivity, myoclonic seizures, and kyphosis. Approximately 10% of male mutants die between 10 and 12 months of age. Heterozygous female mice exhibit a milder phenotype. All mutant male mice and 62% of female heterozygotes exhibit a repetitive clasping movement of their forelimbs and exhibit tremors. The Donating Investigator reports that the myoclonic seizures, kyphosis and reduced survival were observed in aged male mutants on a 129/SvEv genetic background. This mutant mouse strain may be useful in studies of Rett Syndrome.

The Howard Hughes Medical Institute and the National Institutes of Health supported the creation of this model. Importation of this model was supported by the Rett Syndrome Research Foundation.

Development

A targeting vector containing loxP-flanked neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 4, with a stop codon inserted after codon 308. The construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for 12 generations.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Shahbazian M; Young J; Yuva-Paylor L; Spencer C; Antalffy B; Noebels J; Armstrong D; Paylor R; Zoghbi H. 2002. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35(2):243-54PubMed: 12160743 MGI: J:78009

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Genetics

Mecp2^tm1Hzo

Allele Symbol: Mecp2^tm1Hzo

Allele Name	targeted mutation 1, Huda Zoghbi
Allele Type	Targeted (Not Applicable)
Allele Synonym(s)	Mecp2³⁰⁸
Gene Symbol and Name	Mecp2, methyl CpG binding protein 2
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	X
Molecular Note	A stop codon and a floxed neo cassette were inserted into exon 4. The stop codon was inserted downstream of codon 308, allowing translation of the methyl-CpG binding domain and the transcriptional repression domain. Western blot analysis showed that only truncated protein was present in homozygous mutant mice. Staining of brain tissue with a carboxy terminal antibody confirmed the absence of normal protein.
Mutations Made By	Huda Zoghbi, Baylor College of Medicine

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:

Genotype: Mecp2^tm1Hzo related

Neurobiology Research
- Neurodevelopmental Defects
  - Rett's syndrome
- Ataxia (Movement) Defects
- Behavioral and Learning Defects
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^tm1Hzo/Y
involves: 129S7/SvEvBrd * C57BL/6J

behavior/neurological phenotype

abnormal locomotor behavior
- mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds

abnormal motor capabilities/coordination/movement

abnormal social investigation
- in a tube test for social interaction, wild-type mice typically retreated when confronted with mutants, while mutants did not
- total time that wild-type intruder mice spent interacting with mutants is significantly shorter than the time spent interacting with wild-type mice

decreased vertical activity
- although overall level of rearing is not significantly lower, males rear less during the last 10 min interval of testing

hypoactivity
- show normal activity during the first 10 min interval but reduced activity during the second and third 10 min time intervals
- travel shorter distances and spend less time walking in the open-field test

impaired coordination
- exhibit a small impairment in the ability to stay on a modified rotarod (covered with duct tape to eliminate the grips), however do not exhibit defects in forepaw grip strength
- in a vertical pole test, mutants fall off the pole more readily than wild-type
- in a wire suspension test, mutants drop earlier than wild-type
- on a thin horizontal wooden dowel, mutants rapidly lose balance and fall off the dowel
- young mice perform well on motor function tests but become deficient as they age

increased anxiety-related response
- amount of exploratory behavior in the center of the open field does not change during testing like in wild-type mice which increase activity in the center space over time, likely reflecting heightened anxiety

seizures
- spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age

stereotypic behavior
- mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds

tremors
- develop subtle tremors at around 6 weeks of age that worsen with age and are visibly apparent by 4 months of age

cellular phenotype

abnormal cell nucleus morphology
- exhibit histone H3 hyperacetylation in the cerebellum, cerebral cortex, and spleen, indicating that chromatin architecture is abnormal

integument phenotype

disheveled coat
- after 8 months of age, fur is noticeably more disheveled

greasy coat
- after 8 months of age, fur is noticeably more oily

mortality/aging

premature death
- most survive to at least one year of age, however about 10% die after 10 months of age

nervous system phenotype

seizures
- spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age

skeleton phenotype

kyphosis
- 40% develop kyphosis after 5 months of age

Genotype: Mecp2^tm1Hzo/Y
129S7/SvEvBrd-Mecp2

behavior/neurological phenotype

impaired coordination
- in the wire suspension test, young males (8-9 weeks of age drop earlier than wild-type
- performance on a thin horizontal wooden dowel is impaired in older (35-36 weeks of age) but not younger (8-9 weeks of age) males

increased stereotypic behavior
- 100% of males display stereotypic forepaw movements (rapid and repetitive movement of the forelimbs, often bring them together)

tremors
- 100% of males display tremors

Genotype: Mecp2^tm1Hzo/Mecp2⁺
129S7/SvEvBrd-Mecp2

behavior/neurological phenotype

abnormal behavior
- Normal - females display milder and more variable features of Rett Syndrome than males, presumably due to differences in the pattern of X chromosome inactivation
- females display milder and more variable features of Rett Syndrome than males, presumably due to differences in the pattern of X chromosome inactivation

impaired coordination
- females perform as well as wild-type on a thin horizontal wooden dowel, even at 35-39 weeks of age
- in the wire suspension test, females show normal performance at 5-6 weeks of age, but are impaired at older ages (35-39 weeks)

increased stereotypic behavior
- 69% of females display stereotypic forepaw movements (rapid and repetitive movement of the forelimbs, often bring them together)

tremors
- 62% of females exhibit tremors

References

Shahbazian M; Young J; Yuva-Paylor L; Spencer C; Antalffy B; Noebels J; Armstrong D; Paylor R; Zoghbi H. 2002. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35(2):243-54PubMed: 12160743 MGI: J:78009

Additional - Mecp2^tm1Hzo related

Technical Support

CONTACT TECHNICAL SUPPORT

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

Can be maintained female homozygote mated to hemizygote male, this mating scheme tends to have a lower productivy rate. The breeding scheme of heterozygote female mated to hemizygote male increases rate of productivity.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x C57BL/6J (000664)
Citation
When using the Mecp2³⁰⁸ mouse strain in a publication, please cite the originating article(s) and include JAX stock #005439 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<tm1Hzo>

Payment Terms and Conditions

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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

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

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Also Known As:Mecp2308

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Mecp2tm1Hzo

Allele Symbol: Mecp2tm1Hzo

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: Mecp2tm1Hzo related

Mammalian Phenotype Terms by Genotype

Genotype: Mecp2tm1Hzo/Yinvolves: 129S7/SvEvBrd * C57BL/6J

behavior/neurological phenotype

cellular phenotype

integument phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

Genotype: Mecp2tm1Hzo/Y129S7/SvEvBrd-Mecp2

behavior/neurological phenotype

Genotype: Mecp2tm1Hzo/Mecp2+129S7/SvEvBrd-Mecp2

behavior/neurological phenotype

References

Additional - Mecp2tm1Hzo 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

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

Also Known As:Mecp2³⁰⁸

Mecp2^tm1Hzo

Allele Symbol: Mecp2^tm1Hzo

Genotype: Mecp2^tm1Hzo related

Genotype: Mecp2^tm1Hzo/Y
involves: 129S7/SvEvBrd * C57BL/6J

Genotype: Mecp2^tm1Hzo/Y
129S7/SvEvBrd-Mecp2

Genotype: Mecp2^tm1Hzo/Mecp2⁺
129S7/SvEvBrd-Mecp2

Additional - Mecp2^tm1Hzo related