B6;129P2-Mecp2^tm1Bird/J

Stock number: 006847
Product name: Mecp2^lox
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

These floxed mutant mice possess loxP sites flanking exons 3-4 of the Mecp2 gene. This strain may be useful for generating conditional mutations in applications related to neurological and developmental studies of Rett syndrome.

Detailed description

These mice possess two functional loxP sites flanking exons 3-4 of the targeted gene on the X chromosome. Homozygous females and hemizygous males are viable and fertile. Northern blot analysis showed the expected mature transcript from the Mecp2^lox locus. Also detected was an unspliced beta-globin transcript that was introduced into the locus as part of the targeting vector. When these mutant mice are bred to mice that express cre recombinase, resulting offspring will have exons 3-4 deleted in the cre-expressing tissue(s). Mice with this X-linked floxed mutation may be useful in neurological and developmental studies of Rett syndrome.

For example, when crossed to a strain expressing Cre recombinase in nervous tissue (see Stock No. 003771), this mutant mouse strain develops a neurological phenotype that mimics Rett syndrome.

When bred to a strain expressing Cre recombinase in embryonic forebrain GABAergic neurons (see Stock No. 008199 for example), this mutant mouse strain may be useful in studies of diseases related to GABA (gamma-aminobutyric acid)-releasing neurons.

When crossed to a strain expressing Cre recombinase in GABAergic neurons (see Stock No. 017535), these mice exhibit behaviors common to those seen in Rett Syndrome and Autism Spectrum Disorders.

Development

A targeting vector was designed to insert a loxP site upstream of exon 3, as well as a human beta-globin intron 2 and polyadenylation signal followed by a loxp-flanked TK-neo cassette all downstream of the stop codon in exon 4, of the targeted gene. The donating investigator reports that the "middle" loxP site (just 5' of the TK-neo cassette) is non-functional; thus only the loxP sites upstream of exon 3 and downstream of the TK-neo cassette are functional. The construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric offspring were bred to C57BL/6 mice. Heterozygous females (with exons 3-4 flanked by functional loxP sites) were mated with wild-type C57BL/6 animals. The resulting hemizygous males were bred with heterozygous females to generate homozygous females. Homozygous females and hemizygous males were bred together for many generations prior to arrival at The Jackson Laboratory.

Allele

Symbol: Mecp2^tm1Bird
Name: targeted mutation 1, Adrian Bird
MGI accession ID: MGI:2137555
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Mecp2
Marker name: methyl CpG binding protein 2
Chromosome: X
Strain of origin: 129P2/OlaHsd
Molecular note: Insertion of a neomycin resistance cassette into the gene introduced loxP sites that flank exons 3 and 4, and added an intron and polyadenylation signal from the human beta globin gene. From the mutated allele, Northern blot analysis detected the wild type mature transcript and also a transcript in which the beta globin intron was unspliced.