B6.129P2(Cg)-Mecp2^tm4.1Bird/J

Stock number: 026762
Product name: MeCP2-GFP-T158M
Strain synonyms: Mecp2T158M
Research areas: Neurobiology Research, Research Tools

Description

MeCP2-GFP-T158M mice contain the amino acid mutation T158M in exon 4 of the endogenous methyl CpG binding protein 2 gene, and in-frame fused EGFP downstream of the exon 4 coding sequence. This strain may be useful for in studies of Rett syndrome.

Detailed description

The Mecp2 gene is located on the X-chromosome, and exhibits increased expression in the central nervous system during neuronal maturation. Mutations in the MECP2 gene can cause Rett Syndrome, an autism-spectrum neurodevelopmental disorder. These mice express the amino acid mutation T158M in exon 4. Under control of the endogenous Mecp2 promoter, these mice express the MeCP2-EGFP fusion protein in neurons throughout the brain at levels lower than EGFP expression observed in MECP2-EGFP mice (Stock No. 014610). Hemizygous males are viable but not fertile. Males can become phenotypic from 4 weeks of age and have a average survival of 12 weeks. The cause of infertility of hemizygous males has not been determined. Heterozygous females are viable, fertile, and develop a mild progressive phenotype from 4 months of age.

Development

A targeting vector containing an EGFP open reading frame fused to the end of the Mecp2 coding sequence of exon 4 and a loxP site flanked NEO cassette downstream was used to insert the T158M point mutation into exon 4. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were bred to B6.C-Tg(CMV-cre)1Cgn/J mice (Stock No. 006054) to remove the floxed-neo-STOP cassette. The mice were crossed to FVB-Tg (MECP2)1Hzo/J (Stock No. 008679) mice, and were then backcrossed to C57BL/6J for 7 generations. The line no longer contains the Tg(MECP2)1Hzo transgene. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Mecp2^tm4.1Bird
Name: targeted mutation 4.1, Adrian Bird
MGI accession ID: MGI:5529361
Generation method: Targeted
Attributes: Reporter; Null/Knockout; Humanized sequence
Marker symbol: Mecp2
Marker name: methyl CpG binding protein 2
Chromosome: X
Strain of origin: 129P2/OlaHsd
Expressed genes: Mecp2,methyl CpG binding protein 2,mouse, laboratory; GFP,Green Fluorescent Protein,
Site of expression: These mice express the MeCP2-EGFP fusion protein in neurons throughout the brain.
Molecular note: Nucleotide substitution(s) in exon 4 resulted in the amino acid substitution of methionine for threonine at position 158 (T158M). This mutation affects the DNA binding domain. An EGFP was fused in-frame downstream of the coding sequence in exon 4. Cre-mediated recombination removed the floxed neomycin resistance cassette inserted downstream of EGFP. The T158M mutation represents 12% of Rhett Syndrome missense mutations.