B6.129S-Mecp2^tm1Hzo/J

Stock number: 005439
Product name: Mecp2³⁰⁸
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Mecp2³⁰⁸ mice have a loxP-flanked neomycin resistance and herpes simplex virus thymidine kinase genes that disrupt exon 4, with a stop codon inserted after Mecp2 codon 308.

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.

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.

Allele

Symbol: Mecp2^tm1Hzo
Name: targeted mutation 1, Huda Zoghbi
MGI accession ID: MGI:2183727
Generation method: Targeted
Attributes: Not Applicable
Marker symbol: Mecp2
Marker name: methyl CpG binding protein 2
Chromosome: X
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
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.