B6N.129(Cg)-Mecp2^tm1.1Joez/J

Stock number: 017741
Product name: MeCP2 T158A
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Reproductive Biology Research

Description

The amino acid mutation T158A was introduced into exon 4 of the mouse methyl-CpG binding protein 2 (Mecp2) gene, resulting in a phenotypic pattern similar to that observed in patients with Rett Syndrome.

 

Detailed description

These Mecp2^T158A mice contain a missense mutation in exon 4 of the endogenous methyl-CpG binding protein 2 (Mecp2) gene. This mutation introduces the amino acid mutation T158A in the methyl CpG binding domain (MBD) of MeCP2, analogous to a MECP2 mutation found in humans with Rett Syndrome (RTT). RTT is an X-linked neurodevelopmental disorder that can be caused by mutations in the Mecp2 gene. Hemizygous males with the T158A mutation exhibit hypoactivity, poor motor control, irregular breathing, altered anxiety, and impaired learning and memory after 5-6 weeks of age. They are infertile and have a shortened lifespan, with 50% of males dying by 4 months of age. Symptoms in heterozygous females are obvious after 17 weeks of age. Heterozygous females are viable and fertile. The differences seen between the sexes is because Mecp2 is an X-linked gene. Due to X-chromosome inactivation, heterozygous females have mosaic expression of wild-type MeCP2.

Development

A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette upstream of exon 4 of the methyl-CpG binding protein 2 (Mecp2) gene. This mutation introduces the amino acid mutation T158A found in humans carrying the neurodevelopmental disorder Rett Syndrome (RTT). This targeting construct was electroporated into 129Sv derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric males were bred to C57BL/6 females and offspring were bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J transgenic mice (Stock No. 003724) to remove the neo cassette. The resulting offspring were backcrossed to C57BL/6NCrL for at least 10 generations. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6NJ mice (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Mecp2^tm1.1Joez
Name: targeted mutation 1.1, Zhaolan Zhou
MGI accession ID: MGI:5310727
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: MeCP2 T158A; Mecp2^T158A
Marker symbol: Mecp2
Marker name: methyl CpG binding protein 2
Marker synonyms: 1500041B07Rik; AUTSX3; D630021H01Rik; Mbd5; MECP2_e1; MRX16; MRX79; MRXS13; MRXSL; PPMX; RS; RTS; RTT; WBP10
Chromosome: X
Strain of origin: 129
Molecular note: A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette upstream of exon 4. A point mutation was introduced in exon 4, resulting in the amino acid mutation, T158A, found in humans carrying the neurodevelopmental disorder Rett Syndrome (RTT). An additional point mutation was introduced at codon 160 to produce a silent mutation that allowed for identification of targeted ES cells. Cre-mediated recombination removed the neo cassette.