Endocrine Abstracts

Björn Vennström, Karolinska Institute, Stockholm, Sweden AbstractBjörn Vennström obtained his PhD at Uppsala University in 1978. He then spent two years in Dr Michael Bishop's laboratory at UCSF, characterising the erbA and erbB proto-oncogenes. Back in Uppsala he showed that the v-erbB oncogene of the Avian Erythroblastosis Virus is necessary and sufficient for transformation of both hematopoetic ...

T3 is essential for skeletal development and its actions are mediated by two nuclear receptors (TRs), with TR alpha (TRa) being functionally predominant in bone. The TRa1 isoform binds T3 with high affinity and activates target gene expression in response to hormone. TRa2, however, does not bind T3 or regulate transcription in response to hormone. Intriguingly, TRa2 is expressed at high levels from early in development in all tissues and is conserved in all mammals, although i...

T3-receptor alpha (TRa) is the predominant TR isoform in bone. To investigate its function, we analysed mice harbouring a dominant negative R384C mutation in TRa1 (TRa1m/+). The homozygous TRa1m/m mutation is lethal whereas heterozygotes are euthyroid displaying only transient postnatal hypothyroidism. Critically, dominant negative activity of the mutation is overcome by a 10-fold increase in T3, which is achieved by crossing TRa1m/+ mutants wi...

Patients with the syndrome Resistance to Thyroid Hormone (RTH) exhibit purturbances in regulation of serum thyroxine and often suffer from hypermetabolism, tachycardia, hyperactivity and mental retardation. Most of these patients express a mutant thyroid hormone receptor beta (TRb) unable to bind ligand, resulting in transdominant negative effects in transcription. As no patient with a mutant TRa has been identified, we introduced into the mouse TRa1 gene a point mutation foun...