Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Allan-Herndon-Dudley Syndrome: Mechanisms of disease and therapeutic approaches in model organism

Project Coordinator

Leibniz Research Institute for Environmental Medicine (IUF)


Juan Bernal Instituto de Salut Carlos III Madrid, Spain
Lior Appelbaum Bar Ilan University Ramat-Gan, Israel

Allan-Herndon-Dudley syndrome (AHDS) is a rare form of X-linked psychomotor retardation characterized by severe intellectual deficits, pronounced neuromuscular impairments and abnormal thyroid hormone (TH) concentrations. The syndrome is caused by mutations in the SLC16A2 gene encoding the monocarboxylate transporter 8 (MCT8). MCT8 represents a specific TH transporter highly expressed in the CNS and peripheral organs where it facilitates the entry of TH into target cells. Since TH is essential for proper brain development, MCT8 deficiency is considered to result in insufficient neural TH supply and, consequently, in abnormal neural differentiation. The pathogenic mechanisms underlying AHDS, however, are still unknown. We propose to analyze the consequences of MCT8 deficiency on brain maturation in two animal models recently developed in our labs. Whereas Mct8 ko mice lack neurological symptoms due the presence of Oatp1c1, another TH specific transporter in the mouse CNS, Mct8/Oatp1c1 double ko mice faithfully replicate the phenotype of AHDS patients and are, hence, most suited to study central abnormalities due to MCT8 deficiency (WP1). As a second model, MCT8 deficient zebrafish will be used to assess the outcome of MCT8 deficiency neural circuit and formation on behavior and (WP2). The results of these studies will provide the platform for testing therapeutic interventions (WP3). In particular, treatment of animals with TH analogs will reveal to which extent these substances are capable to prevent brain damage and may, thus, be considered as treatment options for AHDS.

E-Rare 2012 - Created by Toussaint Biger