Endocrine Abstracts

Persistent hypomyelination is not only a key symptom of patients with an inactive MCT8 but also represents a prominent feature in mice with a combined inactivation of the thyroid hormone (TH) transporters Mct8 and Oatp1c1 (so-called DKO mice). This phenotype might be explained by an impaired TH passage across the brain barrier cells and consequently, a profound TH deficiency in the CNS of these animals. Alternatively, combined Mct8/Oatp1c1 deletion may result in an impeded TH ...

Gestational hypothyroxinemia (GH) is a common event in human pregnancy generally attributed to iodine deficiency (ID). GH has been associated with the risk of neurodevelopmental defects in the offspring, including autistic traits. However, autistic children are mostly euthyroid, for which the role of thyroid hormones in the phenotype remains under debate.Aim: To generate a mouse model of maternal hypothyroxinemia using moderate ID (mID) in iodine-recycli...

Disturbed brain development and function represents a hallmark of Mct8/Oatp1c1 double knockout (DKO) mice, a well-established mouse model for human MCT8 deficiency. This phenotype can be explained by an impaired TH transport across brain endothelial cells causing a profound brain TH deficiency. Yet, to which extent the brain capillary network formation is compromised in DKO mice has not been elucidated. Here, we examined brain capillary network formation in wildtype, single ko...

Thyroid hormone (TH) action is required for the adequate brain development. While TRα1 is recognized as the predominant receptor mediating most of these effects in brain tissue, the expression of both TRα and TRβ during development prompts further examination on their respective role. The study aims to investigate the role of TRβ during cortical neuron differentiation, taking advantage of induced pluripotent stem cells (iPSCs) obtained from patients with re...

Objectives: Pathogenic variants in monocarboxylate transporter 8 (MCT8, SLC16A2) cause motor and intellectual disability and movement disorder (Allan-Herndon-Dudley Syndrome, AHDS). The mutation affects the transport of thyroid hormones across plasma membranes, including the blood-brain-barrier. While knockout mouse models for Mct8 have allowed important insights into the physiological function of Mct8, most patients are carrying pathogenic missense variants. Recently, an &#14...