Mice, Morphine, and Other Essentials of a Mad Scientist #6

Researching a topic that is fairly untouched proposes additional challenges in comparison to typical school research work. Unlike researching a paper for a class, there are not full length journal articles that discuss the topic, method, and conclusions of what I am studying. Not only is the necessary information scattered across a spectrum of papers but the information can also lead to dead ends. Most recently, I have experienced the latter of these two challenges.

The original proteins that were going to be analyzed were CYP’s 2D6, 2B6, 3A4, and P-Glycoprotein. Each of these proteins has promising research already showing their relevance and importance in human drug interaction. The issue, however, specifically with CYP’s 2D6 and 3A4, is that the protein is not found in naturally grown mice. This problem seems as though it would be picked up on quickly, yet it wasn’t until weeks into researching that we discovered these proteins are not existent in normal mice. The missing details that lead to my misunderstanding of the proteins’ presence in mice are in the type of mice that have been used in the studies I looked at.

While scientists cannot simply test human genes using human subjects, the genes can be tested through the implantation of those genes in other organisms. In studies with “transgenic mice,” researchers take the genes of human DNA and insert them into the DNA of a mouse, in order to have a living organism to run tests with those genes. This, unfortunately, is also the case with CYP’s 2D6 and 3A4. Although often glossed over in the scientific articles, the mice used in research for these two proteins are transgenic, having been grown with the genes for these proteins implanted in their DNA. To our knowledge, the mice from which we are receiving kidneys and livers were not transgenic, therefore not possessing CYP’s 2D6 and 3A4. As much as this is a setback in my work, it is not a complete dead end. There are still the other two proteins to look at, as well as other potential proteins to settle on. On a realistic side, it was beneficial to have discovered the issues with CYP’s 2D6 and 3A4 because the results of testing would have been inconclusive if absent proteins were examined.

Examples of research with transgenic mice:

http://molpharm.aspetjournals.org/content/64/1/42.short

http://molpharm.aspetjournals.org/content/60/6/1260.short

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