B6.Cg-Mbd4^tm1Wed/J

Stock number: 004989
Product name: Mbd4-
Research areas: Cancer Research

Description

These Mbd4 knock-out mice exhibit an increase in average mutation frequency of splenocytes and epithelial cells from the small intestine.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No wildtype gene product (mRNA or protein) is detected by Northern or Western blot analysis. A truncated mRNA is detected at low levels. Splenocytes isolated from homozygotes exhibit a 3-fold increase in average mutation frequency over wildtype. Epithelial cells from the small intestine of homozygotes exhibit a 2-fold increase in average mutation frequency. This mutant mouse strain may be useful in studies of the role of base excision (DNA mismatch) repair in tumorigenesis.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3, which encodes the catalytic domain, and part of intron 3. The construct was electroporated into WW6 embryonic stem (ES) cells (75% 129/Sv, 20% C57BL/6J, 5% SJL). Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for 5 generations (February 2004).

Allele

Symbol: Mbd4^tm1Wed
Name: targeted mutation 1, Winfried Edelmann
MGI accession ID: MGI:2447611
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Mbd4
Marker name: methyl-CpG binding domain protein 4
Chromosome: 6
Strain of origin: STOCK 129/Sv and C57BL/6J and SJL
Molecular note: The gene was disrupted by replacement of exon 3 and part of intron 3 with a PGK-neo cassette via homologous recombination. The targeted mutation results in deletion of the catalytic domain encoded by exon 3. RT-PCR analysis of RNA from homozygous mutant animals confirmed deletion of exon 3 and revealed a low level exon2-exon4 alternative splice product. The predicted product contains a frameshift mutation resulting in a nonfunctional 125 amino acid protein, of which 98 amino acids are Mbd4-derived.