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Using RNA interference to tune gene activity in stem cells

evels of p53 in B-cells by RNAi produces distinct forms of lymphoma. Similar to lymphomas that form in the absence of p53, lymphomas that formed in mice with low p53 levels developed rapidly (reaching terminal stage after 66 days, on average), infiltrated lung, liver, and spleen tissues, and showed little apoptosis or "programmed cell death."

In contrast, lymphomas that formed in mice with intermediate p53 levels developed less rapidly (reaching terminal stage after 95 days, on average), did not infiltrate lung, liver, or spleen tissues, and showed high levels of apoptosis. In mice with high B-cell p53 levels, lymphomas did not develop at an accelerated rate, and these mice did not experience decreased survival rates compared to control mice.

The study illustrates the ease with which RNAi "gene knockdowns" can be used to create a full range of mild to severe phenotypes (something that geneticists dream about), as well as the potential of RNAi in developing stem cell-based and other therapeutic strategies.

Along with a recent study by Hannon and his colleagues that demonstrated germline transmission of RNAi, the current study establishes RNAi as a convenient alternative to traditional, laborious, and less flexible homologous recombination-based gene knockout strategies for studying the effects of reduced gene expression in a wide variety of settings.


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Contact: Peter Sherwood
sherwood@cshl.edu
516-367-6947
Cold Spring Harbor Laboratory
2-Feb-2003


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