Animal model for Parkinson’s disease

At the moment no animal models are available for human Parkinson’s disease. Everyone knows the importance to have right model to study a disease or test drug to care it; this lack must be rapidly overcome, giving the high number of people that suffers for this disease.

Michael J Fox Foundation and Sigma Aldrich set up a rat model in which it was possible to measure neurological damages and show symptomatically what is seen in Parkinson’s disease. Scientists knocked down five genes involved in the disease: leucine-rich repeat kinase 2 (LRRK2), α-synuclein (SNCA), DJ-1 (PARK7), Parkin (PARK2) and PTEN induced putative kinase 1 (PINK1). In this way only genes ownregulated in the disease can be studied, but this is the first step to build more accurate and useful models. They applied the Zinc Finger Nuclease to insert mutations in DNA of one day old rat embryo, then transplanted the embryos into pseudo-pregnant rat and obtain KO offspring. With ZFN technique is possible to eliminate the necessity to bred heterozygous chimeric mice to obtain KO animals. Genetically manipulated rats are now commercially available also for Parkinson’s disease and this opens new challenging opportunities to care this disease.

Nanog and pluripotency

In August 2009 Cell journal published an important article about the role of Nanog in pluripotency. Silva and colleagues showed that Nanog played a crucial role in development of pluripotency in mice. Indeed, they generated a KO mouse for nanog gene and they observed a block in reprogramming cells to achieve the full pluripotency; Nanog re-expression allowed the complete restoration of the reprogramming process indicating the central role of this protein in the acquisition of pluripotency.

Researchers were not able to obtain embryonic stem cell culture from nanog null mice because the embryos didn’t form the inner cell mass and so the pluripotent compartment. Molecular explanation of the role of Nanog is probably related to the signalling pathway that involves also Oct4, it seems that Nanog is important to sustain that pathway by inducing a self maintenance of the system. Nanog is also important for the reactivation of chromosome X, another crucial step to reach the pluripotency. This work increases our knowledge to obtain the induction of pluripotency in vitro: this goal is crucial for instance for many applications of regenerative medicine. Defining the factors that control, start and maintain pluripotency will help us to obtain safer and better induced pluripotent stem cell cultures.