Strain Detail Sheet

Strain Name:
B6J.B6N-Mecp2tm1.1Dhy/Mmucd
Stock Number:
071393-UCD
Citation ID:
RRID:MMRRC_071393-UCD
Other Names:
C57BL/6N-Mecp2

Strain Information

Gene Details

Mecp2tm1.1Dhy
Name: methyl CpG binding protein 2; targeted mutation 1.1, Dag H Yasui
Synonyms: Mecp2-e1-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: Knock-In
Mecp2
Name: methyl CpG binding protein 2
Synonyms: D630021H01Rik, Mbd5, WBP10, 1500041B07Rik
Type: Gene
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: Knock-In
NCBI: 17257
HGNC: HGNC:6990
Homologene: 3657
Genome Browser [Click image to go to Jbrowse]



Additional Resources
IMPC
Google
Entrez
PubMed
IMSR
Gene Ontology
BioGPS
Gene Cloud
IGTC
Mouse Phenome DB
Mouse Mine
KOMP Phenotyping
Monarch
GeneCards
ClinGen
Genetic Alterations
Exon 1 was replaced with a modified exon 1 in which a nucleotide substitution of A to T results in the destruction of the translation initiation site. Flp-mediated recombination removed the FRT-flanked neomycin resistance cassette inserted downstream of the modified exon 1. Western blot analysis confirmed the absence of e1 isoform expression and preserved e2 isoform expression in the brain.
ES Cell Line
JM8.F6

Strain Description

Phenotype
MECP2 (methyl CpG binding protein 2) is an X-linked nucleus protein named for its ability for selectively recognize methylated DNA and repress transcription from methylated gene promoters. The Mecp2 gene is located on the X-chromosome and exhibits increased expression in the brain during development. Mutations in Mecp2 are the major cause of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. The majority of RTT mutations cluster in exons 3 and 4. Approximately 1% of RTT patients have mutations in exon 1. Mecp2-e1 isoform e1 knock-out mice are altered to insert a point mutation (ATG to TTG) in the exon 1 translational start site, the point mutation is an orthologous exon 1 mutation from an RTT patient and results in the absence of exon 1 (isoform e1) but preserve isoform e2 (exon 2) production in the mouse brain. Immunofluorescence and Western blot analysis confirms the absence of isoform e1 and the presence of isoform e2 in all brain regions. Heterozygous females are viable and fertile. Hemizygous males die between 7 and 31 weeks.

Mecp2-e1 hemizygous males exhibit stereotypic overgrooming resulting in hair loss and eventually skin loss on the flanks, chest and tail. In addition, males exhibit altered behavior (reduced anxiety, reduced sociability) progressive motor defects (hindlimb clasping, altered gait and balance), possible seizures, and progressive metabolic defects (increased body fat, hypoactivity, decreased food intake,). Hippocampal neurons in Mecp2-e1 males have smaller nuclei than controls. Heterozygous female mice exhibit milder symptoms including delayed hind limb clasping and metabolic defects (increased body fat, increased liver triglycerides).

MeSH Terms
  • Animals
  • Blotting, Western
  • Exons/genetics
  • Female
  • Fluorescent Antibody Technique
  • Male
  • Methyl-CpG-Binding Protein 2/genetics
  • Mice
  • Mice, Transgenic
  • Mutation/genetics
  • Rett Syndrome/genetics
Strain Development
A BAC construct containing a point mutation (ATG to TTG) in the exon 1 translational start site of the methyl CpG binding protein 2 (Mecp2) gene on the X chromosome. An FRT-flanked neomycin cassette is inserted in intron 1. The construct was electroporated into C57BL/6N-derived JM8.F6 embryonic stem (ES) cells. Resulting ES cells were FLP treated to remove the Neo cassette, and then injected into blastocysts. Resulting chimera were mated to C57BL/6N for germline transmission. Heterozygous mice were later crossed C57BL/6J (~N6) for colony expansions and then inter-crossed for cohort production.
Suggested Control Mice
Wild type siblings or C57BL/6J

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.

Research Applications

  • Models for Human Disease

Strain Origin

Donor
Dag Yasui, Ph.D., University of California Davis.
Janine M. LaSalle, Ph.D., University of California Davis.
Primary Reference

Vogel Ciernia A, Yasui DH, Pride MC, Durbin-Johnson B, Noronha AB, Chang A, Knotts TA, Rutkowsky JR, Ramsey JJ, Crawley JN, LaSalle JM. MeCP2 isoform e1 mutant mice recapitulate motor and metabolic phenotypes of Rett syndrome. Hum Mol Genet. 2018 Dec 1;27(23):4077-4093. doi: 10.1093/hmg/ddy301. (Medline PMCID: 6240741)

Yasui DH, Gonzales ML, Aflatooni JO, Crary FK, Hu DJ, Gavino BJ, Golub MS, Vincent JB, Carolyn Schanen N, Olson CO, Rastegar M, Lasalle JM. Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome. Hum Mol Genet. 2014 May 1;23(9):2447-58. doi: 10.1093/hmg/ddt640. Epub 2013 Dec 18. Erratum in: Hum Mol Genet. 2014 Dec 15;23(24):6695. (Medline PMID: 24352790)

Colony and Husbandry Information

Special Considerations

Mate heterozygous female with wild type male or backcross to C57BL/6J.

Health Status Report

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.

Appearance

Coat Color
Black
Eye
Black

Breeding

MMRRC Breeding System
Random intra-strain mating
Generation
6
Overall Breeding Performance
Good

Reproductive Statistics

NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined X-linked
Homozygotes are fertile: Undetermined X-linked
Hetero/Hemizygotes are fertile: Yes X-linked
Age Reproductive Decline: 7 to 9 months Undetermined
Average litter size
4 to 6
Recommended wean age
4 Weeks
Average Pups Weaned
4 to 6

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

Conditions of Distribution

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*		 Units Notes
071393-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
071393-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.