Description

Strain Information

Type Coisogenic; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Hemizygote x Noncarrier         (Female x Male)   31-MAR-09 Species laboratory mouse Generation F?+F7 (30-MAR-09) Generation Definitions   Donating Investigator Huda Zoghbi,   Baylor College of Medicine

Description
As hemizygotes, these human methyl CpG binding protein 2 transgenic mice express the gene at ~2-fold wildtype levels in the brain. Enhanced motor and contextual learning, and enhanced hippocampal synaptic plasticity phenotypes begin around 10 weeks of age. After 20 weeks of age, the mice progressively develop neurological impairments, seizures, become hypoactive (characterized by a freezing-like behavior), and ~30% die by one year of age. Forepaw clasping, aggressiveness, and kyphosis are also characteristic in these mice. This strain may be useful in studies of X-linked delayed-onset neurobehavioral disorders, including MECP2 duplication syndrome, mental retardation, and autism.

Development
A full-length copy of the human gene was injected into FVB fertilized oocytes. The TG1 line was maintained on the FVB background by the donating investigator.

Control Information

	Control
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of MECP2

008680

FVB-Tg(MECP2)3Hzo/J

View Strains carrying other alleles of MECP2     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tg(MECP2)1Hzo/0

        involves: FVB

• mortality/aging
• premature death
  • 30% of mice die between 20 weeks and 1 year of age; mice surviving past 1 year of age have a normal lifespan   (MGI Ref ID J:94407)
• nervous system phenotype
• *normal* nervous system phenotype
  • no alteration in synaptic release probability is detected in neurons   (MGI Ref ID J:126964)
• • abnormal excitatory postsynaptic currents
    • evoked EPSC amplitudes show a 116% enhancement compared to wild-type   (MGI Ref ID J:126964)
  • abnormal miniature excitatory postsynaptic currents
    • mEPSCs show a significant increase in frequency compared to wild-type   (MGI Ref ID J:126964)
  • abnormal synaptic vesicle number
    • neurons exhibit a 104% enhancement in RRP charge relative to wild-type   (MGI Ref ID J:126964)
  • clonic seizures
    • visually observed as early as 20 weeks of age, with increased frequency by 50 weeks   (MGI Ref ID J:94407)
  • enhanced long term potentiation
    • robust enhancement is observed in mutants   (MGI Ref ID J:94407)
  • enhanced paired-pulse facilitation
    • PPF is greatly enhanced in transgenic mice   (MGI Ref ID J:94407)
  • increased CNS synapse formation
    • in vitro, density of synaptic markers is increased by 60%   (MGI Ref ID J:126964)
    • in vivo, at 2 weeks postnatal, number of glutamatergic synapses is increased by 80%; by 5 weeks, difference is much smaller but is still slightly significant   (MGI Ref ID J:126964)
• behavior/neurological phenotype
• abnormal contextual conditioning behavior
  • in conditioned fear analysis, mutants and wild-type show similar results in cued fear conditioning, but in contextual conditioning, mutants show elevated freezing behavior indicating greater hippocampal learning   (MGI Ref ID J:94407)
• abnormal motor coordination/ balance
  • in dowel test, most animals remain inactive on wooden rod the entire trial period   (MGI Ref ID J:94407)
• • enhanced coordination
    • at 10 weeks of age, transgenics perform better on a rotating rod test on day 2 of training relative to wild-type; upon retesting at 20 weeks, mutants perform significantly better than wild-type   (MGI Ref ID J:94407)
• clonic seizures
  • visually observed as early as 20 weeks of age, with increased frequency by 50 weeks   (MGI Ref ID J:94407)
• decreased anxiety-related response
  • mice show lower anxiety evidenced by increased vertical activity in open field test   (MGI Ref ID J:94407)
• hypoactivity
  • in dowel test, transgenic animals display significantly reduced movement and walk off the length of an elevated dowel fewer times than wild-type   (MGI Ref ID J:94407)
  • characterized by freezing behavior   (MGI Ref ID J:94407)
• increased aggression
  • increased propensity to bite   (MGI Ref ID J:94407)
• increased vertical activity
  • mice show increased vertical activity compared to controls at 10 and 20 weeks   (MGI Ref ID J:94407)
• limb grasping
  • forepaw clasping when lifted by tail   (MGI Ref ID J:94407)
• skeleton phenotype
• kyphosis   (MGI Ref ID J:94407)

View Research Applications

Research Applications

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

Neurobiology Research
Behavioral and Learning Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(MECP2)1Hzo
Allele Name		transgene insertion 1, Huda Y Zoghbi
Allele Type		Transgenic (random, expressed)
Common Name(s)		MeCP2Tg1;
Mutation Made By		Huda Zoghbi,   Baylor College of Medicine
Strain of Origin		FVB
Expressed Gene		MECP2, methyl CpG binding protein 2 (Rett syndrome), human
Promoter		MECP2, methyl CpG binding protein 2 (Rett syndrome), human
Molecular Note		A full-length copy of the human gene was injected into FVB fertilized oocytes. Line 1 (2-fold higher levels of protein compared to endogenous Mecp2) was established. [MGI Ref ID J:94407]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MECP2), Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Collins AL; Levenson JM; Vilaythong AP; Richman R; Armstrong DL; Noebels JL; David Sweatt J; Zoghbi HY. 2004. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13(21):2679-89. [PubMed: 15351775]  [MGI Ref ID J:94407]

Additional References

Tg(MECP2)1Hzo related

Chahrour M; Jung SY; Shaw C; Zhou X; Wong ST; Qin J; Zoghbi HY. 2008. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320(5880):1224-9. [PubMed: 18511691]  [MGI Ref ID J:136439]

Chao HT; Zoghbi HY; Rosenmund C. 2007. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron 56(1):58-65. [PubMed: 17920015]  [MGI Ref ID J:126964]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, hemizygote female x wildtype (or FVB/NJ) male crosses may be used.
Mating System	Hemizygote x Noncarrier         (Female x Male)   31-MAR-09

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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