Stat6 is a protein that activates the transcription of IL-4-stimulated genes. Amino acids critical for Stat6 function were examined in a mutational analysis of the Src homology (SH2) domain of the Stat6 protein. One mutation, substitution of two Alanines for Valine and Threonine in the N-terminal portion of the SH2 domain, produced a constitutively active form of the molecule that did not require IL-4 for activation. This mutant was named Stat6VT. Mice expressing Stat6VT in lymphocytes were generated, and it was found that approximately 10% of the population of Stat6VT mice, a lympho-proliferative disorder (LPD) occurred. In this study, we are examining genes that have a possible role in the development of this proliferative condition. Specifically, we examined the expression levels of Tiam1, Tacstdl, and Gfi-1 and Gfi-1B (genes known to regulate cellular proliferation and survival) in wildtype, normal Stat6VT and Stat6VT/LPD splenocytes by RT-PCR. Tiam1 results were inconclusive, and Tacstdl was not expressed at levels different from those seen in controls. Interestingly, Gfi-1 B, the homolog of Gfi-1, was expressed at increased levels in a specific subpopulation of cells from Stat6VT/LPD mice. Taken together, these data suggest that in cells expressing a constitutively active Stat6, increased expression of Gfi-1B may play a role in the mechanism of lymphoma development. / Department of Biology
| Identifer | oai:union.ndltd.org:BSU/oai:cardinalscholar.bsu.edu:handle/188300 |
| Date | January 2007 |
| Creators | Haffner, Christopher W. |
| Contributors | Bruns, Heather A. |
| Source Sets | Ball State University |
| Detected Language | English |
| Format | xii, 95 leaves : ill. (some col.) ; 28 cm. |
| Source | Virtual Press |
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