ALS mice model contributes the study of ALS

Amyotrophic lateral sclerosis (ALS), also known as Luigarella, is a fatal progressive neurological disease that attacks nerve cells that control free muscles. At present, no effective treatment has been found.

Scientists have been using animal models and recombinant rat proteins to understand the causes of ALS and to conduct therapy tests for decades. Most ALS investigators used a model of a transgenic mouse that mimics clinically worsening in human ALS. However, the model has a serious limitation: there is no expression of TDP-43 protein in the cell at an abnormal site aggregation, while this problem is almost present in all ALS patients. Scientists are concerned that their use of the model will miss vital details.

Now, researchers at the University of Maryland School of Medicine (UM SOM) have for the first time developed two mouse models of the pathology of this protein, TDP-43. The two mouse models also show clinical and pathological features that are visible in many ALS patients. Researchers say the new findings will open up new paths for ALS research, which affects 12,000 Americans a year.

"These new models give us a better chance to understand this disease more precisely and ultimately develop new therapies that will help ALS patients," said Dr. Mervyn Monteiro, professor of anatomy and neurobiology at the UMSOM Center for Biomedical Engineering and Technology. Dr. Monteiro and his colleagues developed these models. The paper was published in the latest issue of the Proceedings of the National Academy of Sciences (PNAS).

Dr. Monteiro has developed a new model by introducing a human gene called ubiquilin2 into mouse DNA. The normal ubiquilin2 gene creates a protein that helps to remove damaged proteins from cells. In the ALS, mutations in the gene produced by the protein can't play this function. Failure to remove damaged proteins can kill cells and cause disease. There is growing evidence that defects in the removal of damaged proteins can lead to neurodegenerative diseases, including ALS.

For three years, Dr. Monteiro and his colleagues have been studying these new ALS mouse models. To ensure that ALS symptoms in mutated mice were due to mutations in ubiquilin 2, the researchers also developed mice bearing the normal human ubiquilin 2 gene. They found that mice carrying the mutant ubiquilin 2 gene developed ALS symptoms and TDP-43 pathology. By contrast, mice carrying the normal version of the gene didn't show these problems. Mutant mice exhibit classical ALS characteristics, including progressive myasthenia gravis and loss of nerve cells that control muscle. These mice also have shorter lifespan than normal mice.

The exact cause of protein accumulation in ALS remains a mystery. However, because it occurs in almost all cases of ALS, scientists believe that it plays an important role in the disease. Dr. Monteiro said new animal models could be used to further understand how defects in protein processing lead to ALS. Ultimately, he says that this new knowledge may help to improve the overall process of removing damaged proteins, stopping or delaying the disease. Flarebio provides recombinant proteins of good quality such as recombinant NPP1 at great prices.