Endocrine Abstracts

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of tumours of the parathyroids, pancreas and pituitary. The MEN1 gene, which is located on chromosome 11q13 and encodes a 610 amino acid protein (menin), belongs to the class of tumour suppressors. To investigate the role of menin in tumour suppression, three different mouse models have been generated through targeted disruption of the Men1 gene. ...

Inbred laboratory mice are widely used to generate, by homologous recombination, transgenic and chemical mutagenesis routes, genetic models of human disease. However, physiological studies of such models are hampered by the lack of normal ranges for serum and urinary biochemistry, particularly in relation to acclimatisation following placement in metabolic cages. To establish such values, we investigated urinary and serum parameters in forty, 24–30 week-old C3H/HeH, BALB/...

Introduction: Patients who have diabetes are at risk of complications, both acutely and in the long term. Although care is individualised, it may not be practical to continuously review this on an individual basis. An audit evaluating outcomes is a useful tool to reflect on multidisciplinary team management. We describe how effective use of resources led to better results in a multi-ethnic population.Population: A total of 130 children and young people w...

Cumulative genetic abnormalities within an oncogenic pathway may contribute to earlier onset or increased aggressiveness of cancers. An example in human and murine cancer is the dysregulation of Wnt signalling by inactivation of the adenomatous polyposis coli (APC) gene that results in accumulation of nuclear β-catenin and earlier onset of renal cell carcinoma, which can be accelerated by p53-deficiency. We therefore investigated the effects of such cumulative genetic abn...

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterised by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumours, is due to mutations of a tumour suppressor gene, MEN1. MEN1 mutations have also been reported to cause familial isolated primary hyperparathyroidism (FIHP). Moreover, 15 identical MEN1 mutations have been reported to cause MEN1 or FIHP in unrelated families; thereby implicating a r...

Renal stone disease is a common disorder for which the underlying causes remain largely unknown. We have investigated a hereditary renal calcification mouse model, Rcalc1, that is not associated with hypercalciuria for underlying mechanisms. Kidney RNA from 30 to 33 week-old Rcalc1 and control BALB/c and C3H female mice (n=4/group) was extracted and hybridised to Mouse Genome 430 2.0 arrays (Affymetrix). Following Robust Multichip Average normalization, pair-wise compar...

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome, an autosomal dominant disorder, is characterised by the occurrence of parathyroid tumours, often carcinomas, and ossifying fibromata of the jaw. The HPT-JT gene, referred to as HRPT2, is located on chromosome 1q25 and consists of 17 exons that encode a 531 amino-acid protein designated parafibromin. To explore the role of HRPT2 in parathyroid tumourigenesis, we generated two mouse models that comprised a conve...

The mouse knockout model for multiple endocrine neoplasia type 1 (MEN1) closely resembles the phenotype of the human disorder, with frequent development of tumours of the parathyroids, pancreas and pituitary. These tumours have loss of heterozygosity (LOH) of the Men1 locus and lack expression of the encoded protein (menin).The aim of this study was to investigate the feasibility of detecting pituitary tumours in heterozygous (Men1+/−...

Vascular calcification, occurring in organs such as heart and kidneys, is associated with increased risk of cardiovascular mortality. The underlying molecular mechanisms remain unknown. To elucidate these, we investigated C3H mice, an inbred strain susceptible to vascular, myocardial and renal calcification. Myocardial calcification in C3H mice involves 4 genetic loci, Dyscalc1-4, that map to chromosomes 7, 4, 12 and 14, respectively. Dyscalc1 contributes to myoc...

This is the first prospective study to compare the efficacy and safety of medical therapy and surgery as primary therapy in acromegaly.A total of 104 patients with untreated acromegaly were enrolled. Eighty-one patients randomized to receive either octreotide LAR 20 mg (n=40) or surgery (n=41) completed the 48 weeks treatment period, and constituted the population used for this analysis, regardless of response to treatment.<p class="abs...