The researchers suspect that the newly identified gene, Cyfip2, determines how mammals respond to cocaine, although it is too soon to tell what the indications are for humans or for addiction, said Dr. Joseph Takahashi, chair of neuroscience and a Howard Hughes Medical Institute investigator at UT Southwestern and the senior author of the study.
The findings, reported in Science, evolved from examining the genetic differences between two substrains of the standard C57BL/6 mouse strain: a “J” strain from the Jackson Laboratory (C57BL/6J) and an “N” strain from the National Institutes of Health (C57BL/6N). Researchers compared the two strains of mice and used their differential responses to cocaine to identify the causative gene.
“We found that the ‘N’ strain has accumulated mutations over time, one of which has a very strong effect on cocaine response,” Dr. Takahashi said. “We propose that CYFIP2 – the protein produced by the Cyfip2 gene – is a key regulator of cocaine response in mammals.”
The Takahashi laboratory has identified about 100 genetic differences that affect protein sequences between the two mouse strains, meaning that there are many genetic differences whose effects are not yet known, he added.
“We identified this gene by first using a forward genetics strategy to search for differences in traits between the two mouse strains. We found a difference in cocaine response between them, with the C57BL/6N strain showing a reduced behavioral response,” Dr. Takahashi said. “We then carried out genetic mapping and whole genome sequencing, which allowed us to pinpoint the Cyfip2 gene as the causative one in a rapid and unambiguous way.”
The C57BL/6J “J” mouse is the gold-standard strain for most research involving the mouse. For example, the reference sequence for the mouse genome, as well as most behavioral and physiological experiments, are based on the “J” strain. However, the International Knockout Mouse Consortium will be shifting emphasis to the “N” strain since they have created 17,000 embryonic stem cell lines with gene mutations that originate from the “N” strain. Thus, identifying genetic differences between these two mouse strains is important, Dr. Takahashi said.
“Although mouse geneticists pay close attention to the specific strains of mice that they use, it has not been generally appreciated that sublines of the same strain of mouse might differ so profoundly. Thus, a ‘C57BL/6’ mouse might appear to be the same, but in fact there are many, many sublines of this laboratory mouse, and it is important to know which exact one you are using. Since the knockout mouse project has produced so many mutations (17,000) derived from the ‘N’ strain, it will be even more important to keep in mind that not all C57BL/6 mice are the same.”
The study was supported by the National Institute on Drug Abuse, by the National Institutes of Health and by the Howard Hughes Medical Institute.
Other UT Southwestern authors include Dr. Vivek Kumar, Instructor; Kyungin Kim, Research Associate; Chryshanthi Joseph, Research Associate; Dr. Saïd Kourrich, Assistant Professor of Psychiatry; and Dr. Hung Chung Huang, Computational Biologist II. Other researchers included Seung-Hee Yoo, former instructor of neuroscience at UT Southwestern and now an assistant professor of biochemistry and molecular biology at UT Health Science Center, Houston; Martha Vitaterna from Northwestern University; Gary Churchill from The Jackson Laboratory; Fernando Pardo-Manuel de Villena from the University of North Carolina at Chapel Hill; and Antonello Bonci from the Intramural Research Program of the National Institute of Drug Abuse / National Institutes of Health.About UT Southwestern Medical Center
Deborah Wormser | Newswise
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences