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Tips from the journals of the American Society for Microbiology
Date:2/16/2011

rds curing genetic blood diseases such as sickle cell anemia and beta-thalassemia. The research is published in the February 2011 issue of the journal Molecular and Cellular Biology.

They also produced for the first time a mouse that synthesizes a distinct fetal-stage hemoglobin, which was necessary for modeling human hemoglobin disorders. These diseases manifest as misshapen hemoglobin, causing anemia, which can be severe, as well as other symptoms, which can range from minor to life-threatening. The cure would lie in causing the body to revert to use of fetal hemoglobin.

"The motivation for our research is to understand the basic mechanisms of gene regulation in order to cure human disease," says Thomas Ryan of the University of Alabama Birmingham, who led the research. "If we can figure out how to turn the fetal hemoglobin back on, or keep it from switching off, that would cure these diseases."

The new model "mimics precisely the timing in humans, completing the switch after birth," says Ryan. "The previous models didn't do that." In earlier models, researchers inserted transgenes, large chunks of DNA containing the relevant genes, randomly into the mouse chromosome. In the new model, the investigators removed the adult mouse globin genes, and inserted the human fetal and adult genes in their places.

The successful engineering of a mouse with a fetal-stage hemoglobin means that humanized mouse models with mutant human genes will not die in utero.

While the basic principals behind the research are simple, the details are complex. For example, Ryan and Sean C. McConnell, a doctoral student who is the paper's first author, had to deal with the fact that hemoglobin switching occurs twice in H. sapiens, from embryonic to fetal globin chains in early fetal life, and then to adult globin chains at birth, while wild type mice have a single switch from embryonic to adult chains early in fetal life. "Instead of
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Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

Page: 1 2 3 4 5 6 7

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