Searchable abstracts of presentations at key conferences in endocrinology

ea0011oc54 | Calcium and bone OC49 Novartis Oncology Young Investigator Award | ECE2006

Adult mice harbouring a dominant negative R384C mutation of TRalpha1 have a marked increase in trabecular bone and micro-mineralisation density

Bassett JHD , Nordstrom K , Vennstrom B , Howell PGT , Boyde A , Williams GR

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...

ea0011p10 | Bone | ECE2006

Thyroid hormone receptor alpha has a critical negative role in maintenance of the adult skeleton

Bassett JHD , O’Shea PJ , Boyde A , Howell PGT , Samarut J , Chassande O , Williams GR

In developmental studies of mice lacking T3-receptor alpha (TRa0/0) and beta (TRb−/−) we demonstrated delayed endochondral ossification, reduced mineralisation and short stature in TRa0/0 mice, despite euthyroidism. In contrast, TRb−/− mice, which display thyroid hormone resistance with elevated T4 and T3 levels, have advanced ossification, increased mineralisation and accelerated growth. T3-target gene studie...

ea0011oc50 | Calcium and bone OC49 Novartis Oncology Young Investigator Award | ECE2006

Congenitally hypothyroid mice with (Pax8−/−) or without (hyt/hyt) functional TSH receptors (TSHR) display equivalent skeletal phenotypes

Williams GR , Swinhoe R , Murphy E , Williams AJ , Costagliola S , Vassart G , Howell PGT , Boyde A , Flamant F , Samarut J , Weiss R , Refetoff S , Bassett JHD

Studies of TSHR−/− mice suggest that TSH inhibits bone turnover, but these mice have congenital hypothyroidism and the actions of TSH cannot be separated from effects of thyroid hormone deficiency. We characterised skeletal development in hyt/hyt mice, which have a point mutation in the Tshr gene, and Pax8−/− mice with thyroid gland agenesis. Hyt/hyt mice have a 100-fold increase in TSH but inactive TSHRs, whereas Pax8&...