FVB/N-Tg(MECP2*R306C/EGFP)1Hzo/J

Stock number: 026044
Product name: MeCP2-R306C
Research areas: Neurobiology Research, Research Tools

Description

These transgenic mice carry an R306C transcriptional repression domain (TRD) mutant form of human MECP2, and are tagged with EGFP. They have been useful in studies of Rett Syndrome (RTT) and MECP2 duplication syndrome.

Detailed description

MECP2 (methyl CpG binding protein 2) is an X-linked transcriptional repressor that binds to methylated CpG dinucleotides. Loss of function causes the progressive neurological disorder Rett Syndrome (RTT). Conversely, duplication or triplication of the chromosomal region causes an equally wide-ranging progressive neurological disorder, MECP2 duplication syndrome, whose features overlap somewhat with RTT.

This transgenic strain expresses full-length human MECP2 carrying an R306C mutation in the transcriptional repression domain (TRD) fused to EGFP. Immunofluorescent methods using anti-MECP2 and anti-GFP antibodies reveal expression patterns throughout the brain that parallel those of the endogenous gene. Transgene expression levels are similar to those of the endogenous X-linked mouse gene.

Hemizygous mice demonstrate no overt phenotype (normal lifespan, body weight, and brain size) on their own, but when put on a Mecp2^-/y background (see Stock No. 005439), they model Rett syndrome with a milder phenotype than the Mecp2 null mice. Compound mutant mice have a shortened lifespan with 50% lethality at 18 weeks (as compared to 11 weeks in Mecp2 null mice) and have smaller brains, motor dysfunction, learning disabilities, increased anxiety, and hypoactivity.

Development

PAC (PAC671D9), containing the entire human MECP2 locus and its essential regulatory elements, was C-terminally tagged with EGFP. An R306C (CGC to TGC) missense mutation in the transcriptional repression domain (TRD) of exon 4 was also introduced. The 99kb PAC was linearized and separated from the backbone by pulse field gel electrophoresis before injection into FVB single cell zygotes. This strain was maintained on an FVB background by the donating lab.

Allele

Symbol: Tg(MECP2*R306C/EGFP)1Hzo
Name: transgene insertion 1, Huda Y Zoghbi
MGI accession ID: MGI:5588452
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(MECP2*R306C/EGFP)1Hzo
Marker name: transgene insertion 1, Huda Y Zoghbi
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: GFP,Green Fluorescent Protein,
Site of expression: MECP2 and GFP are expressed in the brain.
Molecular note: A human PAC (PAC671D9) containing only the MECP2 locus and regulatory elements was modified to introduce a R306C (CGC to TCG) missense mutation in the transcriptional repression domain (TRD) of exon 4 and a C-terminal GFP tag. Expression of the transgene parallels that of endogenous MECP2 in the brain.