Heterozygous Mad2 knock-out mice exhibit an increase in germinal center formation in spleen and a high incidence of lung carcinomas.
Peter K. Sorger, Massachusetts Institute of Technology
Mice that are heterozygous for the Mad2l1tm1Sorg targeted allele are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Homozygous null mice are embryonic lethal; they fail to develop past embryonic days 6-7 due to catastrophic chromosome missegregation and apoptosis. Histological analysis of heterozygous mutant mice reveal increased germinal center formation in spleen and a higher incidence of lung carcinomas when compared to the wildtype. This mutant mouse strain represents a model that may be useful in studies of the role cell-division checkpoints in tumorogenesis.
A targeting vector containing neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter and herpes simplex virus thymidine kinase genes was used to disrupt all coding sequence of the targeted gene. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
|Allele Name||targeted mutation 1, Peter K Sorger|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mad2l1, MAD2 mitotic arrest deficient-like 1|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A PGK-neomycin resistance cassette replaced the entire coding region.|
|Mutations Made By|| |
Max Dobles, Biogen Inc
The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 10 generations (3/02). This strain is maintained as a heterozygote. Homozygous mutant mice have an embryonic lethal phenotype, failing to develop past embryonic days 6-7. Donating Investigator reports reproductive performance of heterozygotes is normal and recommends breeding heterozygotes at approximately 2 months of age; continue to breed for at least 18 months.
When using the Mad2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004372 in your Materials and Methods section.