It is almost impossible to study basic cellular mechanisms in humans. This is why scientists spend so much time trying to find animal models for human diseases. Sometimes, there is a naturally occurring disease in animals that is analogous to a human condition. Other times, the animal’s genome can be modified to replicate mutations that are found in human diseases. However, despite the best efforts of many scientists, models often fail to faithfully replicate all aspects of human disease.
CJD is a prion disease, which means that it is caused by a mis-folded protein. The long chains of amino acids that form proteins must correctly fold themselves to perform their functions. A mis-folded protein can act like a “seed” and cause other proteins to mis-fold and clump together. These large clumps of protein are often more stable than the normally folded protein. They can damage the cells (most often of the brain) and lead to what under the microscope appear to be holes in the brain tissue. When these mis-folded proteins can infect other cells and organisms to cause these clumps to form, they are called prions. Other examples of prion diseases are kuru, mad cow, and scrapie.
In the past, models of CJD were limited to injections of clumps of mis-folded proteins into mice. These mice would develop CJD, but this wasn’t a good model of the spontaneously occurring genetic version of the disease. Other models used genetic tools to express proteins involved in the disease at much higher than normal levels. This is also not the best model because it is hard to interpret the effects of having much more of these proteins in the cell. It’s possible that any effects observed are just due to too much protein bogging down the system. This new model is the most accurate to date, a single amino acid codon change in the mouse’s own genome (meant to replicate a mutation found in humans).
This model replicates all the features of human CJD and is transmissible. The single codon change was made using gene replacement, where the entire gene is cloned in the lab and the specific mutation is induced then this new gene is swapped for the normal copy of the gene in the process of making a new mouse. This manipulation results in models that more closely resemble the human condition. It’s important to consider how closely any animal model truly replicates the human condition. With better models, we may find less failure when potentials treatments are moved into clinical trials.