Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Hemizygote         (Female x Male)   31-JAN-07 Species laboratory mouse Generation N12+N1F13 (13-JUL-09) Generation Definitions   Donating Investigator Huda Zoghbi,   Baylor College of Medicine

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-m32derived 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 Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mecp2

003890	B6.129P2(C)-Mecp2tm1.1Bird/J
007177	B6.129P2-Mecp2tm1Bird/J
006849	B6.129P2-Mecp2tm2Bird/J
018282	B6.Cg-Mapttm1(Mecp2)Jae/LimmJ
006847	B6;129P2-Mecp2tm1Bird/J
017741	B6N.129(Cg)-Mecp2tm1.1Joez/J
016207	B6N.129-Mecp2tm1.1Vnar/J
012602	STOCK Mecp2tm1.1Irsf/J
014610	STOCK Mecp2tm3.1Bird/J

View Strains carrying other alleles of Mecp2     (9 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- 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; RTT

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Angelman Syndrome; AS   (MECP2) Autism, Susceptibility to, X-Linked 3; AUTSX3   (MECP2) Encephalopathy, Neonatal Severe, Due to Mecp2 Mutations   (MECP2) Lubs X-Linked Mental Retardation Syndrome; MRXSL   (MECP2) Mental Retardation, X-Linked, Syndromic 13; MRXS13   (MECP2)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mecp2^tm1Hzo/Mecp2⁺

        129S7/SvEvBrd-Mecp2^tm1Hzo

• behavior/neurological phenotype
• abnormal behavior
  • females display milder and more variable features of Rett Syndrome than males, presumably due to differences in the pattern of X chromosome inactivation   (MGI Ref ID J:78009)
• • impaired coordination
    • in the wire suspension test, females show normal performance at 5-6 weeks of age, but are impaired at older ages (35-39 weeks)   (MGI Ref ID J:78009)
    • females perform as well as wild-type on a thin horizontal wooden dowel, even at 35-39 weeks of age   (MGI Ref ID J:78009)
  • increased stereotypic behavior
    • 69% of females display stereotypic forepaw movements (rapid and repetitive movement of the forelimbs, often bring them together)   (MGI Ref ID J:78009)
  • tremors
    • 62% of females exhibit tremors   (MGI Ref ID J:78009)

Mecp2^tm1Hzo/Y

        involves: 129S7/SvEvBrd * C57BL/6J

• mortality/aging
• premature death
  • most survive to at least one year of age, however about 10% die after 10 months of age   (MGI Ref ID J:78009)
• behavior/neurological phenotype
• abnormal motor capabilities/coordination/movement   (MGI Ref ID J:78009)
• • abnormal locomotor behavior
    • mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds   (MGI Ref ID J:78009)
  • • decreased vertical activity
      • although overall level of rearing is not significantly lower, males rear less during the last 10 min interval of testing   (MGI Ref ID J:78009)
    • hypoactivity
      • travel shorter distances and spend less time walking in the open-field test   (MGI Ref ID J:78009)
      • show normal activity during the first 10 min interval but reduced activity during the second and third 10 min time intervals   (MGI Ref ID J:78009)
  • impaired coordination
    • young mice perform well on motor function tests but become deficient as they age   (MGI Ref ID J:78009)
    • 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   (MGI Ref ID J:78009)
    • in a vertical pole test, mutants fall off the pole more readily than wild-type   (MGI Ref ID J:78009)
    • in a wire suspension test, mutants drop earlier than wild-type   (MGI Ref ID J:78009)
    • on a thin horizontal wooden dowel, mutants rapidly lose balance and fall off the dowel   (MGI Ref ID J:78009)
  • stereotypic behavior
    • mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds   (MGI Ref ID J:78009)
  • tremors
    • develop subtle tremors at around 6 weeks of age that worsen with age and are visibly apparent by 4 months of age   (MGI Ref ID J:78009)
• abnormal social investigation
  • in a tube test for social interaction, wild-type mice typically retreated when confronted with mutants, while mutants did not   (MGI Ref ID J:78009)
  • total time that wild-type intruder mice spent interacting with mutants is significantly shorter than the time spent interacting with wild-type mice   (MGI Ref ID J:78009)
• 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   (MGI Ref ID J:78009)
• seizures
  • spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age   (MGI Ref ID J:78009)
• nervous system phenotype
• seizures
  • spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age   (MGI Ref ID J:78009)
• cellular phenotype
• abnormal cell nucleus morphology
  • exhibit histone H3 hyperacetylation in the cerebellum, cerebral cortex, and spleen, indicating that chromatin architecture is abnormal   (MGI Ref ID J:78009)
• skeleton phenotype
• kyphosis
  • 40% develop kyphosis after 5 months of age   (MGI Ref ID J:78009)
• integument phenotype
• disheveled coat
  • after 8 months of age, fur is noticeably more disheveled   (MGI Ref ID J:78009)
• greasy coat
  • after 8 months of age, fur is noticeably more oily   (MGI Ref ID J:78009)

Mecp2^tm1Hzo/Y

        129S7/SvEvBrd-Mecp2^tm1Hzo

• behavior/neurological phenotype
• impaired coordination
  • 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   (MGI Ref ID J:78009)
  • in the wire suspension test, young males (8-9 weeks of age drop earlier than wild-type   (MGI Ref ID J:78009)
• increased stereotypic behavior
  • 100% of males display stereotypic forepaw movements (rapid and repetitive movement of the forelimbs, often bring them together)   (MGI Ref ID J:78009)
• tremors
  • 100% of males display tremors   (MGI Ref ID J:78009)

View Research Applications

Research Applications

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

Mecp2^tm1Hzo related

Mouse/Human Gene Homologs
Rett syndrome

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mecp2tm1Hzo
Allele Name		targeted mutation 1, Huda Zoghbi
Allele Type		Targeted (knock-out)
Common Name(s)		Mecp2308;
Mutation Made By		Huda Zoghbi,   Baylor College of Medicine
Strain of Origin		129S7/SvEvBrd-Hprt
ES Cell Line Name		AB2.2
ES Cell Line Strain		129S7/SvEvBrd-Hprt
Gene Symbol and Name		Mecp2, methyl CpG binding protein 2
Chromosome		X
Gene Common Name(s)		1500041B07Rik; AUTSX3; BB130002; D630021H01Rik; MRX16; MRX79; MRXS13; MRXSL; Mbd5; PPMX; RIKEN cDNA 1500041B07 gene; RIKEN cDNA D630021H01 gene; RS; RTS; RTT; WBP10; expressed sequence BB130002;
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 onlytruncated protein was present in homozygous mutant mice. Staining of brain tissue with a carboxy terminal antibody confirmed the absence of normal protein. [MGI Ref ID J:78009]

Genotyping

Genotyping Information

Genotyping Protocols

Mecp2^{tm1 Hzo} MCA SEP,

Separated MCA

Mecp2^tm1Hzo, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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):243-54. [PubMed: 12160743]  [MGI Ref ID J:78009]

Additional References

Mecp2^tm1Hzo related

Alvarez-Saavedra M; Saez MA; Kang D; Zoghbi HY; Young JI. 2007. Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis. Hum Mol Genet 16(19):2315-25. [PubMed: 17635839]  [MGI Ref ID J:124365]

Caballero IM; Hendrich B. 2005. MeCP2 in neurons: closing in on the causes of Rett syndrome. Hum Mol Genet 14 Spec No 1:R19-26. [PubMed: 15809268]  [MGI Ref ID J:97524]

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]

De Filippis B; Ricceri L; Laviola G. 2010. Early postnatal behavioral changes in the Mecp2-308 truncation mouse model of Rett syndrome. Genes Brain Behav 9(2):213-23. [PubMed: 19958389]  [MGI Ref ID J:170055]

Deng JV; Rodriguiz RM; Hutchinson AN; Kim IH; Wetsel WC; West AE. 2010. MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants. Nat Neurosci 13(9):1128-36. [PubMed: 20711186]  [MGI Ref ID J:165279]

Gambino F; Khelfaoui M; Poulain B; Bienvenu T; Chelly J; Humeau Y. 2010. Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. PLoS One 5(7):e11399. [PubMed: 20625482]  [MGI Ref ID J:163122]

Hu B; Gharaee-Kermani M; Wu Z; Phan SH. 2011. Essential Role of MeCP2 in the Regulation of Myofibroblast Differentiation during Pulmonary Fibrosis. Am J Pathol 178(4):1500-8. [PubMed: 21435439]  [MGI Ref ID J:169859]

McGill BE; Bundle SF; Yaylaoglu MB; Carson JP; Thaller C; Zoghbi HY. 2006. Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A 103(48):18267-72. [PubMed: 17108082]  [MGI Ref ID J:117154]

Moretti P; Bouwknecht JA; Teague R; Paylor R; Zoghbi HY. 2005. Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Hum Mol Genet 14(2):205-20. [PubMed: 15548546]  [MGI Ref ID J:95512]

Moretti P; Levenson JM; Battaglia F; Atkinson R; Teague R; Antalffy B; Armstrong D; Arancio O; Sweatt JD; Zoghbi HY. 2006. Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J Neurosci 26(1):319-27. [PubMed: 16399702]  [MGI Ref ID J:104113]

Palmer A; Qayumi J; Ronnett G. 2008. MeCP2 mutation causes distinguishable phases of acute and chronic defects in synaptogenesis and maintenance, respectively. Mol Cell Neurosci 37(4):794-807. [PubMed: 18295506]  [MGI Ref ID J:135669]

Palmer AM; Degano AL; Park MJ; Ramamurthy S; Ronnett GV. 2012. Normal mitral cell dendritic development in the setting of Mecp2 mutation. Neuroscience 202:108-16. [PubMed: 22138506]  [MGI Ref ID J:184408]

Semaan SJ; Dhamija S; Kim J; Ku EC; Kauffman AS. 2012. Assessment of epigenetic contributions to sexually-dimorphic kiss1 expression in the anteroventral periventricular nucleus of mice. Endocrinology 153(4):1875-86. [PubMed: 22374971]  [MGI Ref ID J:183767]

Watson CM; Pelka GJ; Radziewic T; Shahbazian MD; Christodoulou J; Williamson SL; Tam PP. 2005. Reduced proportion of Purkinje cells expressing paternally derived mutant Mecp2308 allele in female mouse cerebellum is not due to a skewed primary pattern of X-chromosome inactivation. Hum Mol Genet 14(13):1851-61. [PubMed: 15888476]  [MGI Ref ID J:105061]

Young JI; Zoghbi HY. 2004. X-chromosome inactivation patterns are unbalanced and affect the phenotypic outcome in a mouse model of rett syndrome. Am J Hum Genet 74(3):511-20. [PubMed: 14973779]  [MGI Ref ID J:89295]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	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.
Mating System	Heterozygote x Hemizygote         (Female x Male)   31-JAN-07
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

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