Gaining a Better Understanding of Kidney Diseases
By introducing a genetic switch in mice it is possible to increase or decrease the production of specific protein molecules in their kidneys. Thus, researchers can study the influence of specific proteins on disease development. Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg University Hospitals and other research institutes have published this model of investigating severe kidney diseases in the latest issue of Nature medicine.
Cystic kidney disease, renal fibrosis, or renal cell carcinoma: Many diseases of the excretory organs are characterized by overproduction or – on the contrary – absence of characteristic proteins in the renal cells. An international research team under the leadership of scientists from DKFZ and Heidelberg University Hospitals has now developed an animal model to better investigate these conditions.
The researchers introduced a genetic switch into the genome of mice. This switch allows to selectively turn on and off the production of disease-typical proteins in renal tissue. It is activated simply by adding the antibiotic tetracycline to the animal food.
To find out whether it is possible to study the development of kidney diseases in the genetically modified (transgenic) animals, the investigators stimulated the production of c-Myc in the renal tissue of the mice. Numerous tumors have been reported to be associated with elevated levels of this transcription factor. Shortly after activation of the c-Myc gene the animals started developing cysts that led to organ failure. Pathologists also discovered renal cell carcinomas in some of the mice. As a reaction to the overexpression of another signaling molecule, the mice developed renal fibrosis.
Earlier attempts to study disease development using transgenic animals have often failed because the proteins to be studied are overproduced in the murine embryos already. As a result, the animals often develop severe malformations that make meaningful conclusions impossible. “A particular advantage of our model is that we can switch on and off disease-typical renal proteins at any given time,” explained Associate Professor (PD) Dr. Robert Kösters of the Institute of Human Genetics of the University of Heidelberg and Professor Dr. Hermann-Josef Gröne of the German Cancer Research Center. “Thus, we are able to simulate the natural course of disease development and also of healing processes.”
Milena Traykova-Brauch, Kai Schönig, Oliver Greiner, Tewfik Miloud, Anna Jauch, Manja Bode, Dean W Felsher, Adam B Glick, David J Kwiatkowski, Hermann Bujard, Jürgen Horst, Magnus von Knebel Doeberitz, Felix K Niggli, Wilhelm Kriz, Hermann-Josef Gröne and Robert Koesters: An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nature medicine, 24 August 2008
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.