Kliniken & Institute ... Institute Humangenetik Forschung Abt. Molekulare... Synaptic proteins SHANK... FOXP1 in intellectual...


Intellectual disability (ID) is a highly heritable disorder and sometimes co-segregates with other developmental disorders, such as speech and language disorder. For many patients, both language disorders and intellectual disability are caused by genetic defects and the identification of these genetic factors paves the way to understanding the underlying biological pathways and neurological mechanisms of the disorder.
The first and best known gene associated with language disorders is the Forkhead Box P2 (FOXP2) gene. FOXP2 is one of four members of the FOXP subfamily of forkhead box transcription factors. We have identified deletions of the related FOXP1 gene in three patients with intellectual disability and significant impairment of speech and language abilities (Horn et al., 2010). This finding indicates that the transcription factor FOXP1, very similar to FOXP2, might play an important role during brain development. Unlike FOXP2, very little is known about how FOXP1 regulates these processes. The goal of our project is to characterize the role of FOXP1 in brain development and to identify the genes that represent the downstream targets of this protein in neuronal differentiation. We are using a conditional Foxp1 knockout mouse to investigate brain development in the absence of Foxp1 and to identify targets of Foxp1.

Horn, D.*, Kapeller, J.*, Bruguès, N.R., Moog, U., Lorenz-Depiereux, B., Eck, S., Hempel, M., Wagenstaller, J., Gawthorpe, A., Monaco, A.P., Bonin, M., Riess, O., Wohlleber, E., Illig, T., Agnes-Studie, Franke, A., Spranger, S., Villavicencio Lorini, P., Seifert, W., Rosenfeld, J., Klopocki, E., Rappold, G.A.*, Strom, T.A.* (* equal contribution) (2010) Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits. Hum. Mutat. 31:E1851-60.