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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First in the No. 2 Business

June 13, 2014

By Medical Discovery News

Antibiotic resistance among disease-causing bacteria is a growing and dangerous problem. Bacteria resistant to one or antibiotics, like Staph and Strep, are approaching catastrophic levels. Bacteria so resistant to common antibiotics that few if any drugs are available to treat them have been dubbed superbugs. One widely feared bacterium, called Clostridium difficle or C. diff for short, causes intestinal disease so severe that it can become life-threatening. It kills almost 15,000 Americans every year, mostly the elderly. Super-resistant forms of this microbe are almost impossible to treat with antibiotics. 

This bacterium produces a powerful toxin that destroys intestinal cells and can rupture small blood vessels. It also causes abnormal intestinal behavior, mainly excess water that produces diarrhea. It’s an unpleasant and painful prospect for those infected with C. diff. 

Roughly 5-15 percent of the population carries this bacterium in their digestive system naturally, but it is kept in check by the rest of the bacterial population. But an underlying disease, antibiotics, another infection, or chemotherapy can weaken bacterial systems, allowing C. diff to expand into an infection. And a super-resistant version of C. diff can be a real problem.

As gross as it may sound, fecal transplants are getting lots of attention as an option for C. diff infections. First tried in the late 1950s, the rationale for this approach is that the disease occurs because the bacterial populations are disrupted, so providing a source of normal bacteria restores the ecology of the intestine and prevents C. diff from growing. 

Where exactly does one find fecal matter for such a transplant? It’s not as if anyone wants to ask family or friends to share their poop. Actually, there are major regulatory obstacles for fecal transplants. For instance, the fecal source must test negative for disease-causing bacteria, viruses, and parasites. Basically, it’s not something anyone can find at Whole Foods or on Amazon.

So a group of enterprising graduate students at the Massachusetts Institute of Technology (MIT) who observed a friend’s struggle with C. diff formed a company to distribute safe, certified fecal matter for transplant. OpenBiome collects, tests, and distributes fecal matter like a blood bank distributes blood. Samples are certified by Food and Drug Administration (FDA) procedures, which cost about $3,000. Then they are frozen at super-cold temperatures (-112 degrees) and shipped to hospitals and physicians. Currently, the company operates as a nonprofit and only collects a shipping and processing fee for transplant material.

We already know that our normal bacterial systems, which together make up our microbiome, help protect us from skin, urogenital, and oral diseases. Changes in our microbiome may also contribute to an underlying disease like diabetes. There is still much to be discovered about these organisms that call our bodies home, especially since we house 10 times more microbes than our own cells!

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