Friday, September 17, 2010

Nicotine and the Humphrey Bogart Gene

You can lead a fish to water, but can you make it smoke?

Zebrafish embryo showing axon tracts in green, viewed from lateral (top) and dorsal (bottom) orientations------>

Common denizens of home aquariums, the humble zebrafish may dart about the tank like any other small tropical specimen, but zebrafish have become one of the hot genetic research tools of the moment. The lab rat may have met its match in the lab zebrafish, a popular non-mammalian organism that is currently playing a leading role in government-sponsored research on the genetic aspects of nicotine addiction.

Scientists are fond of these new fishy animal models because zebrafish are cheap, develop rapidly, and are more biologically similar to humans than anyone might naively assume. Their transparent embryos allow researchers to inject flourescent proteins into living animals, and in some cases to track the regulation of gene expression as it is happening.
affecting nicotine exposure. Like rats, the fish show characteristic behaviorial responses to low doses, high doses, and the nicotine sensitization process. According to NIDA, the scientists “induced mutations in particular DNA segments of the zebrafish and looked at changes in the nicotine response profile of mutant carriers compared to their siblings.” The changes in nicotine response observed between the groups were mediated by two genes, which the scientists dubbed bdav/cct8 (bette davis) and hbog/gabbr1.2 (humphrey bogart), named after “celebrities that suffered from tobacco-related cancers.” These two genes, when expressed, caused zebrafish to respond more positively to nicotine.

“We all know how hard it is to quit smoking,” Dr. Ekker told Mayo’s online research magazine, Discovery’s Edge. “What most people don’t know is that genetic differences significantly contribute to the degree of nicotine dependence. We want to understand the genetics behind different responses to nicotine and come up with more effective and individualized treatments for people addicted to nicotine.”

The Mayo Clinic in Minnesota has taken a leading role in developing the fish for research, having established the Zebrafish Core Facility in 2007 under the direction of Dr. Stephen Ekker. Mayo’s zebrafish are now being used in various research laboratories for research in the fields of developmental biology and functional genomics. The fish are now a crucial part of biological research on cancer and heart disease, as well as addiction.

Graphics Credit:

Petzold AM, Balciunas D, Sivasubbu S, Clark KJ, Bedell VM, Westcot SE, Myers SR, Moulder GL, Thomas MJ, & Ekker SC (2009). Nicotine response genetics in the zebrafish. Proceedings of the National Academy of Sciences of the United States of America, 106 (44), 18662-7 PMID: 19858493

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