These Tob1 knock out mice are suitable for use in applications related to the study of cell proliferation and tumor suppression.
Jaime Modiano, University of Minnesota Cancer Center
The Tob1 (transducer of ErbB-2.1) gene encodes for an anti-proliferative protein that interacts with the erbB-2 receptor tyrosine kinase. These mice carry a knock out mutation of the Tob1 gene in which a PGK-NEO cassette replaced the single coding exon. Mice that are homozygous for the targeted mutation are viable and fertile. Dystocia frequently occurs in homozygous female X homozygous male and heterozygous female X homozygous male crosses. Homozygous and heterozygous females often exhibit defective lactation, requiring pup fostering.
No gene product (protein) is detected by Western blot analysis of primary embryonic fibroblasts.
The Donating Investigator reports that homozygous mice in his colony do not develop spontaneous tumors up to 20 months of age, and do not exhibit any grossly apparent increase in bone density. The original paper describing the strain (Cell. 2000 Dec 22;103(7):1085-97) describes homozygotes at 18 months of age develop more spontaneous tumors when compared to wildtype controls. In addition, previous characterization of the strain includes: homozygotes at 2 months of age exhibit increased bone mass, increased trabecular bone, enhanced bone formation rate, and accelerated hepatocyte proliferation and restoration of liver mass after hepatectomy. Mutant mice are more susceptible to developing carcinogen induced tumors. The Donating Investigator reports that homozygotes have hyper-proliferative T cells.
A targeting vector containing a PGK-NEO cassette was used to disrupt the single coding exon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to female C57BL/6 mice. Heterozygotes were intercrossed to generate homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Tadashi Yamamoto|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Tob1, transducer of ErbB-2.1|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A PGK-neomycin resistance cassette was inserted into the only exon of the gene. Western blot analysis of primary embryonic fibroblasts detected only one of the two wild-type forms of the protein in homozygous mutant mice. Northern blot analysis did not detect transcript in osteoblast lineage cells derived from calvariae of homozygous mutant newborns. Also, BMP2-stimulated DNA synthesis was enhanced in these cells compared to wild-type.|
When maintaining a live colony, these mice can be bred by heterozygous crosses. Dystocia frequently occurs in homozygous female X homozygous male and heterozygous female X homozygous male crosses. Homozygous and heterozygous females often exhibit defective lacation, requiring pup fostering.
When using the B6;129S4-Tob1tm1Tya/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #023346 in your Materials and Methods section.