Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2014

Oral Communications

Thyroid and bone

ea0034oc4.1 | Thyroid and bone | SFEBES2014

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 exert dominant-negative effects

Howles Sarah , Nesbit M Andrew , Hannan Fadil , Rogers Angela , Piret Sian , Rust Nigel , Thakker Rajesh

Adaptor protein-2 (AP2) is a heterotetramer of α, β, μ, and σ subunits that is pivotal in clathrin-mediated endocytosis and facilitates internalisation of plasma membrane constituents such as the calcium-sensing receptor (CaSR). AP2 σ subunit (AP2σ) missense mutations (Arg15Cys, Arg15His and Arg15Leu) result in familial hypocalciuric hypercalcaemia type 3 (FHH3) and decrease the sensitivity of CaSR-expressing cells to changes in extracellular calc...

ea0034oc4.2 | Thyroid and bone | SFEBES2014

PHOSPHO1: roles beyond skeletal mineralisation

Oldknow Karla , Morton Nik , Yadav Manisha , Rajoanah Sophie , Huesa Carmen , Bunger Lutz , Ball Derek , Ferron Mathieu , Karsenty Gerard , MacRae Vicky , Luis Millan Jose , Farquharson Colin

Advances in genetic approaches to bone physiology have expanded our understanding of the mechanisms by which bone and energy homeostasis interact. PHOSPHO1, a bone specific phosphatase is essential for the initiation of bone mineralisation. Here we now show that Phospho1 ablation confers a remarkable protection against obesity and diabetes in mice. To understand the mechanism whereby Phospho1 impacts metabolism, microarray analysis of osteoblasts, the primary...

ea0034oc4.3 | Thyroid and bone | SFEBES2014

TRα mutation causes a severe and thyroxine-resistant skeletal dysplasia

Bassett J H Duncan , Boyde Alan , Zikmund Tomas , Evans Holly , Croucher Peter I , Zhu Xuguang , Park Jeong Won , Cheng Sheue-yann , Williams Graham R

A new genetic disorder has recently been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio, constipation and a variable intellectual deficit, but exhibit a consistently severe skeletal dysplasia. Similar to these patients, Thra1PV/+ mice harbour a mutation that disrupts the C-terminal α-helix of TRα1 and express a domi...

ea0034oc4.4 | Thyroid and bone | SFEBES2014

Thyroid hormones stimulate osteoclastogenesis via TRα-dependent actions in osteoblasts

Logan John G , Bassett J H Duncan , Williams Graham R

Thyrotoxicosis results in osteoporosis and thyroid hormone (T3) stimulates osteoclastic bone resorption by unknown mechanisms. We previously demonstrated that knockout mice lacking thyroid hormone receptor α (TRα0/0) are euthyroid but have high bone mass, whereas mice lacking TRβ (TRβ−/−) are thyrotoxic and have osteoporosis. Tartrate resistant acid phosphatase (TRAcP) staining revealed osteoclast numbers were re...

ea0034oc4.5 | Thyroid and bone | SFEBES2014

A mutation in the 5′-UTR of GNA11 causes familial hypocalciuric hypercalcemia type 2 due to reduced translational efficiency

Howles Sarah , Nesbit MAndrew , Hannan Fadil , Piret Sian , Cranston Treena , Rahman Mushtaqur , Thakker Rajesh

The calcium-sensing receptor (CaSR) is a guanine-nucleotide-binding protein (G-protein)-coupled receptor that has a central role in calcium homeostasis. Loss-of-function mutations of the CaSR result in familial hypocalciuric hypercalcemia type 1 (FHH1) and loss-of-function coding mutations in the CaSR-associated G-protein subunit Gα11 have been reported to cause FHH2 in only two patients to date. The aim of our study was therefore to characterise additional <em...

ea0034oc4.6 | Thyroid and bone | SFEBES2014

An ENU-induced Tyr265Stop mutation in Polg2 is associated with renal calcification in RCALC2 mice

Gorvin Caroline , Piret Sian , Ahmad Bushra , Stechman Michael , Loh Nellie , Hough Tertius , Leo Paul , Marshall Mhairi , Sethi Siddharth , Bentley Liz , Reed Anita , Christie Paul , Simon Michelle , Mallon Ann-Marie , Brown Matthew , Cox Roger , Brown Steve , Thakker Rajesh

Renal calcification (nephrocalcinosis), which has a multi-factorial etiology involving environmental and genetic determinants, affects ~8% of adults by 70 years. Nephrocalcinosis may occur as a familial disorder in ~65% of patients, and in 70% of patients, nephrocalcinosis may be associated with endocrine and metabolic disorders that include primary hyperparathyroidism, renal tubular acidosis, hypercalciuria, cystinuria, and hyperoxaluria. Investigations of families with hered...