MEGAP

In the past few years research on genetic causes of mental retardation has made a lot of progress. Mental retardation is defined as retardation of the mental development that manifests itself in delayed cognitive, linguistic and social skills. About 3% of the population is affected by different degrees of severity of mental retardation, which can be measured by means of ntelligence tests. It is our goal to determine and characterize genes with defects leading to mental retardation.

One of these genes which in a mutated form – leads to a defective connection of brain cells (neurons), is the Mental disorder-associated GAP protein, MEGAP Functional analyses have shown that MEGAP plays an important role in both formation and locomotion of neurons.

Besides molecular genetic and neurobiologicaltechniques, we have eveloped in cooperation with the Central Institute of Mental Health (CIMH Mannheim) – an animal (mouse) model simulating a genetic mutation, which has originally been found in man. With the aid of this model, we intend to determine the exact mechanisms leading to mental retardation in patients suffering from this genetic defect.

Endris, V., Wogatzky, B., Leimer, U., Bartsch, D., Tariverdian, G., Kirsch, S., Karch, D., Rappold, G.A.: The novel Rho-GTPase activating gene MEGAP has a role in severe mental retardation. PNAS 99:11754-11759, 2002.

Yang Y, Marcello M, Endris V, Saffrich R, Fischer R, Trendelenburg MF, Sprengel R, Rappold G.MEGAP impedes cell migration via regulating actin and microtubule dynamics and focal complex formation. Exp Cell Res. 2006 Jul 15;312(12):2379-93. Epub 2006 Apr 19. 

Bacon C, Endris V, Andermatt I, Niederkofler V, Waltereit R, Bartsch D, Stoeckli ET, Rappold G.Evidence for a role of srGAP3 in the positioning of commissural axons within the ventrolateral funiculus of the mouse spinal cord.PLoS One. 2011;6(5):e19887. Epub 2011 May 31.