Humanizing the Mouse

March 20, 2015

By Medical Discovery News

Humanizing the Mouse

In the 1986 horror movie “The Fly,” a scientist’s teleportation experiment goes awry when a fly lands in one of the teleportation pods and he undergoes a transformation into a part fly, part human monster. Today, science has given us the capability to create animal-human hybrids, although so far none of them has craved human flesh like they tend to do in the movies.

Neuroscientists at the Massachusetts Institute of Technology (MIT) have been introducing human genes into mice to study the effects on mouse brain function and capabilities. They are doing this in small steps, using genetic engineering techniques to introduce a specific, single human gene into a mouse. This will allow scientists to evaluate the impact of each human gene on the brain in another species. It’s not quite a monstrous Franken-mouse, but the results have definitely been revealing.

The human version of gene Fox2p is connected with language and speech development, a trait associated with the higher order brain function unique to humans. When this gene was introduced into mice in the experiment, they developed more complex neurons and more extensive circuits in their brains. Scientists wondered if this gene is responsible for the enhanced brain and cognitive abilities displayed in humans.

In the behavioral experiments at MIT, scientists placed mice in a maze and evaluated the reactions of mice harboring the Fox2p gene versus normal mice. The maze offered two modes of navigation to the mice: visual clues in the environment that were observable from within the maze and tactile clues in the pathways of the maze consisting of smooth or textured floor.

The hybrid mice learned to navigate the maze quickly, finishing it three times faster than normal mice. This cognitive enhancement or flexibility reflects the human capability of handling and processing information. The tactile information is handled by something called procedural or unconscious learning. However, the sight-derived clues represent declarative learning. It is the addition of the Fox2p gene that gave mice the ability to integrate both forms of learning.

Interestingly, if the visual clues or the tactile clues were removed, the hybrid mice did no better than the normal mice at navigating the maze. This might mean that the hybrid mice only performed better when they could utilize both forms of information. This ability to switch between and consider different forms of memory (procedural and declarative) is important and may explain in part why it is so important in human speech and language development.

Humanized animals are being used in a number of scientific fields to help us understand different elements of human physiology. Expect to see more of the humanization of animals in the future, but alas for you Sci-Fi fans – a Frankenmouse is not yet on the horizon.

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And The Winners Are

Jan. 3, 2014

By Medical Discovery News

The Nobel Prize

Inside each living cell is a complex system of roadways, each used to transport molecules so the cell can keep performing the processes it was made to do. Like highways that span from one state to another, cells can even use the roadways to deliver molecules to other cells. How cells are able to do this has been an intense area of study for years, and thanks to three Nobel prize-winning scientists, it’s a little more understood now.

This year’s Nobel Prize for Physiology or Medicine was awarded to scientists who have unraveled the mysteries of how cells route or traffic specific molecules to the correct locations.  The $1.4 million prize was split between Drs. James Rothman of Yale University, Randy Schekman of University of California-Berkeley, and Thomas Sudhof of Stanford University. Their work revealed a basic element of cell physiology that is essentially the same for all cells, from single-celled yeasts to complex mammals like humans.

The basic mode of transporting molecules in cells is in a vesicle – hollow, spherical structures that carry molecules inside. Molecules are packaged at different places in cells and then safely transported at the right time to the correct destination via vesicles. But how does this transportation container know where to drop off its delivery? With mail, a zip code is written on the outside of a letter specifying a precise location where it is to be delivered. With vesicles, there are specific proteins on the outside surface of the sphere that specify where its cargo is to be delivered, whether it’s within a cell or to the cell’s surface, to be released from the cell to other cells. With the right cellular zip code, molecules are delivered to the right place.

Schekman discovered the genes and proteins that regulate these vesicles. They are the traffic cops that control vesicle traffic through the cells. He found that different genes and proteins determined whether a vesicle delivered its contents to the cell’s surface or to different compartments inside a cell. While he studied this in yeast cells, similar genes and proteins have been found in more complex animals such as mice and humans.

Rothman found the specific proteins on the surfaces of vesicles that represent molecular zip codes and allow the vesicles to interact with proteins at their correct destinations. The interaction between these two groups of complementary proteins causes the vesicle to fuse with the membrane at its intended destination and release its contents.

Sudhof revealed how nerve cells communicate with each other and how calcium ions control this activity. He found that calcium ions act as a trigger, causing vesicles to fuse with cell surfaces and release the molecules to interact with neighboring cells, transmitting signals along a nerve.

This transportation system is used for critical functions in humans, like brain signals and immune responses, so problems within the system can cause disease. These pioneers have provided an incredible understanding upon which others can continue to build.

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