Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Hemizygote         (Female x Male) Species laboratory mouse Generation ?+N2F4 (11-NOV-08)   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
006847	B6;129P2-Mecp2tm1Bird/J
006849	B6;129P2-Mecp2tm2Bird/J

View Strains carrying other alleles of Mecp2     (4 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Rett Syndrome; RTT - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

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

Mecp2^tm1Hzo/Y

        involves: 129S7/SvEvBrd * C57BL/6J

• life span-post-weaning/aging
• premature death (MGI Ref ID J:78009)
  • most survive to at least one year of age, however about 10% die after 10 months of age
• behavior/neurological phenotype
• abnormal motor capabilities/coordination/movement (MGI Ref ID J:78009)
• abnormal involuntary movement (MGI Ref ID J:78009)
  • mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds
• tremors (MGI Ref ID J:78009)
  • develop subtle tremors at around 6 weeks of age that worsen with age and are visibly apparent by 4 months of age
• abnormal locomotor activity (MGI Ref ID J:78009)
  • mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds
• decreased vertical activity (MGI Ref ID J:78009)
  • although overall level of rearing is not significantly lower, males rear less during the last 10 min interval of testing
• hypoactivity (MGI Ref ID J:78009)
  • travel shorter distances and spend less time walking in the open-field test
  • show normal activity during the first 10 min interval but reduced activity during the second and third 10 min time intervals
• impaired coordination (MGI Ref ID J:78009)
  • young mice perform well on motor function tests but become deficient as they age
  • 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
• abnormal social investigation (MGI Ref ID J:78009)
  • 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
• increased anxiety-related response (MGI Ref ID J:78009)
  • 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 (MGI Ref ID J:78009)
  • spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age
• nervous system phenotype
• seizures (MGI Ref ID J:78009)
  • spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age
• cellular phenotype
• abnormal nucleus morphology (MGI Ref ID J:78009)
  • exhibit histone H3 hyperacetylation in the cerebellum, cerebral cortex, and spleen, indicating that chromatin architecture is abnormal
• skeleton phenotype
• kyphosis (MGI Ref ID J:78009)
  • 40% develop kyphosis after 5 months of age
• skin/coat/nails phenotype
• disheveled coat (MGI Ref ID J:78009)
  • after 8 months of age, fur is noticeably more disheveled
• greasy coat (MGI Ref ID J:78009)
  • after 8 months of age, fur is noticeably more oily

Mecp2^tm1Hzo/Y

        129S7/SvEvBrd-Mecp2^tm1Hzo

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

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

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-Hprt1
ES Cell Line Name		AB2.2
ES Cell Line Strain		129S7/SvEvBrd-Hprt1
Gene Symbol and Name		Mecp2, methyl CpG binding protein 2
Chromosome		X
Gene Common Name(s)		1500041B07Rik; AUTSX3; BB130002; D630021H01Rik; DKFZp686A24160; MRX16; MRX79; MRXS13; MRXSL; Mbd5; PPMX; RIKEN cDNA 1500041B07 gene; RIKEN cDNA D630021H01 gene; 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^tm1Hzo, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

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)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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