FVB/N-Tg(MECP2*R111G/EGFP)1Hzo/J

Stock number: 026045
Product name: MeCP2-R111G
Research areas: Neurobiology Research, Research Tools

Description

These transgenic mice carry an R111G methyl-CpG binding domain (MPD) 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.

These transgenic mice express full-length human MECP2 carrying an R111G mutation in the methyl-CpG binding domain (MPD) 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 the Mecp2 null phenotype. Compound mutant animals develop behavioral symptoms of Retts around 4-6 weeks of age and die prematurely (median lifespan is 11 weeks).

Development

PAC (PAC671D9), containing the entire human MECP2 locus and its essential regulatory elements, was C-terminally tagged with EGFP. An R111G (AGG to GGG) missense mutation in the methyl-CpG binding domain (MPD) of exon 3 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*R111G/EGFP)1Hzo
Name: transgene insertion 1, Huda Y Zoghbi
MGI accession ID: MGI:5588460
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(MECP2*R111G/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 R111G (AGG to GGG) missense mutation in the methyl-CpG binding domain (MPD) of exon 3 and a C-terminal GFP tag. Expression of the transgene parallels that of endogenous MECP2 in the brain.