|
Model Characteristics - Model:
Tip30 knockout
|
| Model Descriptor |
Tip30 knockout
|
| Official Nomenclature |
|
| Genotype |
|
| Species |
Mouse (Mus musculus)
|
| Strain |
129
|
| Is This a Tool Strain? |
No
|
Developmental Stage
(applies only to Zebrafish) |
|
| Experimental Design |
To isolate the mouse Tip30 gene, a mouse 129SvJ genomic library was screened with a mouse Tip30 cDNA probe. Fourteen overlapping clones contained a 49-kb genomic region that included five coding exons of the Tip30 gene locus. The HindIII-SacI 2.7-kb genomic fragment was replaced by LacZ in-frame and a phosphoglycerate kinase neo-cassette. This replacement ablated the two exons that encode the NH2-terminal portion of TIP30, except for 10 amino acids after the translation start site. The targeting vector included a 5.2-kb upstream homologous region and a 6.5-kb downstream region. E14 embryotic stem (ES) cells were electroporated with the linearized targeting vector and selected with geneticin on embryonic fibroblast feeder cells as described previously. In total, 348 G418-resistant clones were screened by Southern blot analysis using the 5' external probe, and 65 clones displayed evidence for the homologous recombination of the disrupted Tip30 gene. Ten ES clones were microinjected into blastocysts of C57BL6/J female mice. Germ-line chimeras were bred to C57BL6J mice to generate heterozygous mutant F1 mice.
|
| Phenotype |
TIP30, also called CC3 or Htatip2, is a putative metastasis suppressor that promotes apoptosis and inhibits angiogenesis. Although TIP30 has several characteristic features of a tumor suppressor in in vitro analyses, tumor development as a result of TIP30 inactivation has not been demonstrated in vivo, and abnormal expression of TIP30 in human cancer has not been reported. Using genetically engineered mice and cells deficient in TIP30, we show that TIP30-deficient mice have a high incidence of hepatocellular carcinoma and other tumors, and loss of TIP30 enhances susceptibility of fibroblasts to transformation by the SV40 large T antigen. Furthermore, immunohistochemical analysis indicates that reduced TIP30 expression is associated with 33% of human hepatocellular carcinomas. Some of these carcinomas harbor missense mutations in the Tip30 gene, which cause abnormal expression of TIP30. Together, these results demonstrate that the Tip30 gene is a tumor susceptibility gene playing an important role in the suppression of hepatocarcinogenesis
|
| Website for add. info |
|
| Breeding Notes |
|
| Sex Distribution of the Phenotype |
|
| Submitted by |
Xiao, Hua
|
| Principal Investigator / Lab |
Xiao, Hua
|
| Comment |
|
| |
| Model Availability: This model is available from |
| Strain |
Distributor |
Stock number |
|
| |
 Comments (Please login to submit new comments) |
|
