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THE EFFECT OF A TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT (EKER) RATS.
Citation:
Sen, B., S D. Hester, AND D C. Wolf. THE EFFECT OF A TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT (EKER) RATS. Presented at AACR Workshop, Pathobiology of Cancer, Keystone, Colorado, 07/13-20/03.
Description:
Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting for up to 80% of malignant renal neoplasms. Hereditary RCC in the Eker rat, which bear a number of cellular, molecular and phenotypic similarities to human RCC, results from an inherited insertional mutation in the Tsc2 tumor suppressor gene. The utility of the Eker rat model is in studying potential renal carcinogens, providing a valuable experimental model to characterize the function of the Tsc2 gene product, tuberirl and to elicit the mechanisms of tumorigenesis caused by the Tsc2 gene inactivation. We propose the hypothesis that multiple pathways will be affected by the knocking out of a specific gene involved in turnorigenesis in the rat kidney. Gene expression was analyzed to determine the transcriptional profile as a consequence of the Tsc2 mutation using Agilent' EDNA arrays containing 14,000 rat genes. Total RNA from wild type (+/+) and heterozygous mutant (+/-) rats was reverse transcribed into CDNA using standard techniques. The two dye labeling protocol was used to incorporate fluorescent tags into the CDNA. The data was generated using an Axon scanner and analysis performed with the GeneSpring7 analysis software. Preliminary data suggests that the basal expression level of genes involved in pathways up and downstream of known and suspected tuberin activity, namely Rab5, rho B and cdc42 were up regulated by two fold in the mutant rats. The overall pattern of gene expression between the wild-type and mutant rat kidneys was different, however a significant number of these changes were associated with genes involved in tuberin related activities.
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