STOCK Mecp2^tm1.1Irsf/J

Stock number: 012602
Product name: Mecp2*R225X
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Mecp2*R255X mice contain a mutation in the Mecp2 gene, similar to that found in humans with Rett Syndrome (RTT).

Detailed description

These Mecp2*R255X mice contain the amino acid mutation R255X in exon 4 of the endogenous methyl CpG binding protein 2 (Mecp2) gene. This mutation introduces a premature stop codon within the transcription repression domain-nuclear localization signal region, analogous to a Mecp2 mutation found in humans with Rett Syndrome (RTT). Female carriers are viable and fertile while male hemizygotes have a reduced life span. RTT is a neurodevelopmental disorder which can be caused by point mutations in the Mecp2 gene. Mecp2 is located on the X-chromosome, and exhibits increased expression in the central nervous system during neuronal maturation. Female carriers of the R255X mutation may develop normally or may exhibit a mild phenotype including some obesity, reduced coordination, and lethargy. This is presumably in part due to inactivation of the X-chromosome and the presence of a compensatory wildtype X-chromosome. Hemizygous males develop a severe neurological phenotype. Specifically, males begin to develop hindlimb clasping and exhibit excessive weight gain by 3 weeks of age, being up to 10g heavier than their littermates. They also display behavior defects such as pauses, abnormal gait, and impaired coordination. These mice may be useful for studying impaired neurodevelopmental maturation associated with human RTT.

Development

A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette downstream of exon 3 of the methyl CpG binding protein 2 (Mecp2) gene. A point mutation was introduced in exon 4, corresponding to human amino acid 255, resulting in a non-sense mutation, R255X, commonly found in humans carrying Rett Syndrome (RTT). This targeting construct was electroporated into 129Sv/Pas-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to females carrying Cre-recombinase on a C57BL/6 background to remove the floxed selection cassette. Female Mecp2*R255X mice, lacking the floxed neo cassette, were then crossed to male B6129SF1/J (Stock No. 101043). Upon arrival at The Jackson Laboratory, mutant mice were bred to B6129SF1/J mice for at least one generation to establish the colony.

Allele

Symbol: Mecp2^tm1.1Irsf
Name: targeted mutation 1.1, International Rett Syndrome Foundation
MGI accession ID: MGI:4830980
Generation method: Targeted
Attributes: Null/Knockout; Humanized sequence
Synonyms: Mecp2*R255X
Marker symbol: Mecp2
Marker name: methyl CpG binding protein 2
Marker synonyms: 1500041B07Rik; AUTSX3; D630021H01Rik; Mbd5; MRX16; MRX79; MRXS13; MRXSL; PPMX; RS; RTS; RTT; WBP10
Chromosome: X
Strain of origin: 129S2/SvPas
Molecular note: A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette downstream of exon 3 of the methyl CpG binding protein 2 (Mecp2) gene. A point mutation was introduced in exon 4, corresponding to human amino acid 255, resulting in a non-sense mutation, R255X, commonly found in humans carrying Rett Syndrome (RTT). Cre mediated recombination removed the floxed selection cassette. Western blot analysis indicates absence of full-length protein or the predicted truncation product.