JAX Mouse Strain Datasheet - 005439

B6.129S-Mecp2^tm1Hzo/J

Stock No:: 005439 |; Mecp2³⁰⁸

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Overview

Also Known As: Mecp2³⁰⁸

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
	N12+N5 (07-APR-17)

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

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Base Price

Starting at:

$224.00 Domestic price for female

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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):243-54. PubMed: 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)	1500041B07Rik; 1500041B07Rik; AUTSX3; BB130002; D630021H01Rik; D630021H01Rik; MRX16; MRX79; MRXS13; MRXSL; Mbd5; PPMX; RIKEN cDNA 1500041B07 gene; RIKEN cDNA D630021H01 gene; RS; RTS; RTT; WBP10; expressed sequence BB130002
Strain of Origin	129S7/SvEvBrd-Hprt
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

Research Areas By Genotype

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

Genotype: Mecp2^tm1Hzo related

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

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

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/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

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

nervous system phenotype

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

skeleton phenotype

kyphosis
- 40% develop kyphosis after 5 months of age

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

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):243-54. PubMed: 12160743 MGI: J:78009

Additional - 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: 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: 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: J:94407
De Felice C; Della Ragione F; Signorini C; Leoncini S; Pecorelli A; Ciccoli L; Scalabri F; Marracino F; Madonna M; Belmonte G; Ricceri L; De Filippis B; Laviola G; Valacchi G; Durand T; Galano JM; Oger C; Guy A; Bultel-Ponce V; Guy J; Filosa S; Hayek J; D'Esposito M. 2014. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome. Neurobiol Dis 68:66-77. PubMed: 24769161 MGI: J:214008
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: J:170055
Delepine C; Meziane H; Nectoux J; Opitz M; Smith AB; Ballatore C; Saillour Y; Bennaceur-Griscelli A; Chang Q; Williams EC; Dahan M; Duboin A; Billuart P; Herault Y; Bienvenu T. 2016. Altered microtubule dynamics and vesicular transport in mouse and human MeCP2-deficient astrocytes. Hum Mol Genet 25(1):146-57. PubMed: 26604147 MGI: J:227619
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: 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: 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: J:169859
Hulbert SW; Jiang YH. 2016. Monogenic mouse models of autism spectrum disorders: Common mechanisms and missing links. Neuroscience 321:3-23. PubMed: 26733386 MGI: J:232349
Kloth AD; Badura A; Li A; Cherskov A; Connolly SG; Giovannucci A; Bangash MA; Grasselli G; Penagarikano O; Piochon C; Tsai PT; Geschwind DH; Hansel C; Sahin M; Takumi T; Worley PF; Wang SS. 2015. Cerebellar associative sensory learning defects in five mouse autism models. Elife 4:e06085. PubMed: 26158416 MGI: J:225991
Lombardi LM; Baker SA; Zoghbi HY. 2015. MECP2 disorders: from the clinic to mice and back. J Clin Invest 125(8):2914-23. PubMed: 26237041 MGI: J:225796
Matagne V; Budden S; Ojeda SR; Raber J. 2013. Correcting deregulated Fxyd1 expression ameliorates a behavioral impairment in a mouse model of Rett syndrome. Brain Res 1496:104-14. PubMed: 23246925 MGI: J:206550
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: 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: 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: 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: 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: J:184408
Ratnam S; Engler P; Bozek G; Mao L; Podlutsky A; Austad S; Martin T; Storb U. 2014. Identification of Ssm1b, a novel modifier of DNA methylation, and its expression during mouse embryogenesis. Development 141(10):2024-34. PubMed: 24803651 MGI: J:213590
Schwartzer JJ; Koenig CM; Berman RF. 2013. Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions. Neurotoxicol Teratol 36:17-35. PubMed: 23010509 MGI: J:221700
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: 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: J:105061
Woods R; Vallero RO; Golub MS; Suarez JK; Ta TA; Yasui DH; Chi LH; Kostyniak PJ; Pessah IN; Berman RF; LaSalle JM. 2012. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Hum Mol Genet 21(11):2399-411. PubMed: 22343140 MGI: J:232470
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: J:89295

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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

Research Areas By Genotype

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

Genotype: Mecp2tm1Hzo related

Mammalian Phenotype Terms by Genotype

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

behavior/neurological phenotype

Genotype: Mecp2tm1Hzo/Y129S7/SvEvBrd-Mecp2tm1Hzo

behavior/neurological phenotype

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

mortality/aging

behavior/neurological phenotype

nervous system phenotype

cellular phenotype

skeleton phenotype

integument phenotype

References

Additional - Mecp2tm1Hzo related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

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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/Mecp2⁺
129S7/SvEvBrd-Mecp2^tm1Hzo

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

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

Additional - Mecp2^tm1Hzo related