International Research Fellowship Program: Assessing the Role of Perlecan for Basement Membrane Function and Cartilage Formation Using Transgenic Mice

Rodgers Kathryn D, Omaha NE

Investigators

Abstract

0205057 Rodgers The International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twenty-four month research fellowship by Dr. Kathryn D. Rodgers to work with Dr. Reinhard Fassler at Max Planck Institute of Biochemistry in Martinsreid, Germany. This project will provide valuable information about the different roles of proteoglycans in basement membrane development and how they compensate each other functionally. The first goal is to cross heterozygous mice to generate agrin/perlecan knockouts to assess the roles of these proteins in development and to clarify the results from the single knockouts. The second is to analyze whether perlecan expression has an effect on cartilege development and collagen fibril development. The PI will generate mice expressing perlecan under control of the type II collagen promotor, and then to cross these mice with the perlecan-null mice. Detailed EM-level analysis together with biochemical methods will be used to assess the collagens that are formed. The third goal is to use Cre/loxP system to develop a mouse with a deleted IG3 module of domain IV of perlecan, as well as antibodies to detect the IG2/IG4 recombinant molecule. This will address more specifically the portion of the perlecan molecule that has particular functions, with a great level of molecular detail. In addition to Dr. Fassler, the PI will work with Drs. Rupert Timpl, Max Planck Institute, Anders Aspberg, Lund University in Lund, Sweden, and Peter Bruckner, Westfalische Wilhelms Universitat Munster, in Munster, Germany.