Searchable abstracts of presentations at key conferences in endocrinology

ea0025oc4.1 | Bone and diabetes | SFEBES2011

A mouse with an ENU-induced mutation (Tyr209Asn) in the natriuretic peptide receptor 3 (Npr3) develops autosomal recessive kyphosis

Esapa Christopher , Head Rosie , Thomas Gethin , Brown Matthew , Croucher Peter , Cox Roger , Brown Steve , Thakker Rajesh

Kyphosis is a common spinal disorder affecting up to 8.3% of the population, and associated with significant morbidity. Familial and twin studies have implicated a genetic involvement. However, the causative genes have not been identified. Studies investigating the underlying molecular mechanisms are hampered by genetic heterogeneity, small families and variable modes of inheritance displayed by different kindreds. To overcome these limitations, we investigated 12 week old pro...

ea0025p17 | Bone | SFEBES2011

A 5′-untranslated region mutation of the growth and differentiation factor 5 (Gdf5) gene increases expression and is associated with decreased urinary excretion of the cartilage degradation product, CTX-II: relevance to osteoarthritis

Nesbit M Andrew , Esapa Chris , Head Rosie , Gaynor Katie , Cox Roger , Brown Steve , Thakker Rajesh

Osteoarthritis (OA) may be associated with endocrine disorders such as hypothyroidism, obesity, primary hyperparathyroidism or acromegaly, although often its cause remains undefined. To facilitate investigations of the underlying molecular mechanisms of OA we have investigated N-ethyl-N-nitrosourea (ENU) mutant mice using a genotype-driven approach in which candidate genes are examined for mutations. One such investigated gene is growth and differentiation factor...

ea0021oc2.2 | Neuroendocrine tumours/pituitary | SFEBES2009

Wnt/β-catenin signalling is down-regulated in pituitary tumours from a multiple endocrine neoplasia type 1 (MEN1) mouse model

Walls Gerard , Newey Paul , Nesbit M Andrew , Jeyabalan Jeshmi , Schulz Herbert , Huebner Norbert , Thakker Rajesh

The tumour suppressor menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, has been reported to be a component of the Wnt/β-catenin signalling pathway. To investigate the effects of menin loss on this pathway, we have determined the cDNA expression profiles of pituitary tumours from 5 Men1+/− mice and in normal pituitaries from 5 Men1+/+ littermates by extracting total RNA and by hybridizing it to Affymetrix Mous...

ea0021oc3.4 | Young Endocrinologists prize session | SFEBES2009

MicroRNAs, let-7 and miR-302, have an altered expression in Men1-null embryos, consistent with abnormal embryonic development

Bowl Michael , Newey Paul , Reed Anita , Walls Gerard , Baban Dilair , Nesbit Andrew , Thakker Rajesh

The multiple endocrine neoplasia type 1 (MEN1) gene, which when mutated gives rise to parathyroid, pancreatic and pituitary tumours, has been shown to have a role in embryogenesis, as Men1-null mice (Men1−/−) are embryonic lethal by 12.5 days post coitum (dpc). MicroRNAs (miRNAs) are emerging as potent regulators of early mammalian embryogenesis, and we therefore undertook expression profiling of miRNAs in Men1+/+ and M...

ea0021p16 | Bone | SFEBES2009

A novel GATA3 mutation, Tyr345Cys, in hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome results in abolished DNA binding

Grigorieva Irina , Gaynor Katie , Cranston Treena , McWilliam Catherine , Ahmed Faisal , Nesbit M Andrew , Thakker Rajesh

GATA3 mutations cause the congenital autosomal dominant hypoparathyroidism, Deafness and Renal dysplasia (HDR) syndrome. GATA3 belongs to a family of dual zinc-finger transcription factors that recognise the consensus (A/T)GATA(A/G) motif and are involved in vertebrate embryonic development. We investigated a HDR proband for GATA3 abnormalities. Venous blood was obtained after informed consent, as approved by the local ethical committee, and leukocyte DNA extracted. GATA3 spec...

ea0021p158 | Diabetes and metabolism | SFEBES2009

Nuf mice with an activating calcium sensing receptor mutation, Leu723Gln, have a metabolic acidosis and impaired urinary acidification

Hannan Fadil , Nesbit M Andrew , Esapa Chris , Di Pretoro Simona , Lyon Mary , Cox Roger , Thakker Rajesh

The calcium sensing receptor (CaSR) is a G protein coupled receptor that is expressed in type A intercalated cells of the distal convoluted tubule and cortical collecting ducts, where it is involved in renal proton excretion. We have therefore investigated the Nuf mouse, which has an activating CaSR mutation (Leu723Gln) that leads to hypocalcaemia, hypercalciuria, renal calcification, a urinary concentrating defect, and cataracts, for disturbances in acid-base homeostasis. Mic...

ea0021p166 | Diabetes and metabolism | SFEBES2009

Nuf mice with an activating calcium-sensing receptor mutation, Leu723Gln, have impaired glucose tolerance and reduced insulin secretion

Hannan Fadil , Nesbit M Andrew , Bentley Liz , Cox Roger , Thakker Rajesh

The calcium-sensing receptor (CaSR) is a G protein coupled receptor that is expressed widely, including pancreatic beta cells where it has been shown to modulate insulin secretion in vitro. However, the role of the CaSR in regulating in vivo insulin secretion and glucose homeostasis remains unknown. We have therefore investigated the Nuf mouse, which has an activating CaSR mutation (Leu723Gln), to determine whether abnormal CaSR function in vivo affects gl...

ea0021p177 | Diabetes and metabolism | SFEBES2009

Mice harbouring the familial juvenile hyperuricaemic nephropathy disease-causing uromodulin (Tamm--Horsfall glycoprotein) mutation Cys125Arg, have a urine concentrating defect, progressive renal failure, and altered uric acid handling

Piret Sian , Reed Anita , Nesbit M Andrew , Hough Tertius , Bentley Liz , Cox Roger , Thakker Rajesh

Familial juvenile hyperuricaemic nephropathy (FJHN), an autosomal dominant disorder characterised by raised serum urate, reduced fractional excretion of uric acid (FEUA), a urine concentrating defect, and progressive renal failure, is caused by mutations in the UMOD gene, encoding uromodulin (Tamm–Horsfall glycoprotein). The FJHN-causing UMOD mutations are missense mutations (>90%) or inframe deletions (<10%), and none result in prematurely truncated...

ea0021p214 | Endocrine tumours and neoplasia | SFEBES2009

Mutations of the transcription factor, GATA3, in oestrogen receptor positive breast cancers

Gaynor Katherine , Grigorieva Irina , Esapa Chris , Head Rosie , Christie Paul , Nesbit Andrew , Jones Louise , Thakker Rajesh

Mutations of the transcription factor GATA3, which is important for maintaining human breast luminal epithelial cell differentiation and quiescence, have been reported in 17 oestrogen receptor (ER) positive breast cancers, although the functional effects of these mutations have not been studied. We therefore investigated 56 ER-positive breast cancers for GATA3 mutations. The tumours were macrodissected, and immunohistochemistry for GATA3 revealed a strong correlation between E...

ea0021p233 | Growth and development | SFEBES2009

A novel dominant-negative Glial Cells Missing B (GCMB) mutation (Asn502His) is associated with autosomal dominant hypoparathyroidism and results in reduced transactivation activity

Bowl Michael , Mirzcuk Samantha , Fratter Carl , Cranston Treena , Allgrove Jeremy , Brain Caroline , Nesbit Andrew , Thakker Rajesh

Glial cells missing B (GCMB), which is the mammalian homologue of the Drosophila GCM gene, encodes a 506 amino acid parathyroid-specific transcription factor that contains: a DNA-binding domain (residues 21–174); a predicted nuclear localization signal (residues 176–193); an inhibitory domain (residues 258–347); and two transactivation domains (residues 174–263, and residues 428–506). To date only two different GCMB m...