Erstellen einer Knockout Maus als Modell für die X-gekoppelte lymphoproliferative Erkrankung und Analyse des SH2D1A Gens auf eine mögliche Tumorsuppressorfunktion an Non-Hodkin-Burkitt Tumor Zellinien

• Antragsteller: Dr. Oliver Brandau
• Fachliche Zuordnung: Humangenetik
• Förderung: Förderung von 2000 bis 2002
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5239331

The SH2D1A gene is mutated in about 70 % of X-linked lymphoproliferative disease (XLP) patients and also in Epstein-Barr Virus (EBV) negative patients with early onset non-Hodgkin Burkitt lymphoma (NHBL). SH2D1A codes for an SH2-domain protein, which inhibits the activation of a signalling cascade regulating proliferation and differentiation of B- and T-cells. The occurrence of SH2D1A mutations in patients with early onset NHBL, independent of EBV infection, suggests a tumor suppressor function for the SH2D1A gene. I will create an SH2D1A-null mouse to serve as a model for XLP and to study the downstream signalling from SH2D1A. To investigate the functional properties of this gene in terms of tumor propagation a NHBL cell line from an XLP patient will be established and transfected with SH2D1A. Overexpression of proteins inhibited by SH2D1A in NHBL lines BJAB, CA46 and MC116 is proposed, to analyse if these proteins are involved in the high malignancy of NHBLs with a duplication of chromosome 1q23-25.

• DFG-Verfahren: Forschungsstipendien