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PATHOLOGY OF THREE TRANSGENIC MOUSE LINES WITH UNIQUE PTEN MUTANT ALLELES

Naidu, Shan Krishnan
http://rave.ohiolink.edu/etdc/view?acc_num=osu1282941122

Abstract Details

2010, Master of Science, Ohio State University, Veterinary Biosciences.
Pten is a tumor suppressor gene frequently mutated in human cancers. Pten is a dual specific phosphatase which dephosphorylates both lipid and protein substrates. While the role of lipid phosphatase activity of Pten in mediating tumor suppression through the PI3K-AKT pathway is well established, the role of its protein phosphatase is inconclusive. Cowden Syndrome patients have germline mutation in Pten gene and exhibit a range of clinical syndrome and cancer susceptibility. The relationship between type of Pten mutation and organ-specific susceptibility to develop cancer has not yet been established. We studied the tumor phenotype in mice with G129E mutation which is reported to retain protein phosphatase activity of Pten while losing lipid phosphatase activity, and compared the results with C124R mutant mice which is expected to lose both lipid and protein phosphatase activity, and Pten knockout mice. We used 40 mice in each group and analyzed the tumor spectrum by complete necropsy and histopathological examination at 9 months of age. We found that each point mutation in Pten had a distinct tumor spectrum. Each mutant allele had a gender bias in promoting tumorigenesis in an organ-specific manner. PtenG129E/+ mice are highly prone to develop high grade proliferative lesions in the thyroid, prostate and mammary glands compared to PtenC124R/+ mice. Interestingly our analysis showed that the proliferative lesions in PtenG129E/+ mice continued to express normal levels of Pten, while the lesions in PtenD4–5/+ and PtenC124R/+ mice lost wild-type Pten expression. In addition, our results show that loss of heterozygosity (LOH) is not always required for tumor initiation in all three groups of Pten mutant mice. We speculate that the higher incidence of proliferative lesions in specific organs of PtenG129E/+ mice could be attributed to a gain of function mutation and recruitment of an AKT-independent pathway in tumorigenesis.
Thomas Rosol (Committee Chair)
Michael Ostrowski (Committee Co-Chair)
Gustavo Leone (Advisor)
James DeWille (Committee Member)
100 p.
Genetics; Pathology
pten; pathology; knockin; knockout; mouse models; phenotyping; cowden syndrome; cancer

Recommended Citations

Citations

  • Naidu, S. K. (2010). PATHOLOGY OF THREE TRANSGENIC MOUSE LINES WITH UNIQUE PTEN MUTANT ALLELES [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1282941122

    APA Style (7th edition)

  • Naidu, Shan. PATHOLOGY OF THREE TRANSGENIC MOUSE LINES WITH UNIQUE PTEN MUTANT ALLELES. 2010. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1282941122.

    MLA Style (8th edition)

  • Naidu, Shan. "PATHOLOGY OF THREE TRANSGENIC MOUSE LINES WITH UNIQUE PTEN MUTANT ALLELES." Master's thesis, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1282941122

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.