Mapping of the calcium-sensing receptor gene (CASR) to human Chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat Chromosome 11 and mouse Chromosome 16

Janicic, Nataša; Soliman, Eric; Pausová, Zdenka; Seldin, Michael F.; Riviere, Michèle; Szpirer, Josiane; Szpirer, Claude; Hendy, Geoffrey N.

doi:10.1007/bf00539007

Cited by 114 publications

(41 citation statements)

References 27 publications

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“…The human CASR gene is located on chromosome 3q13.3-21 (4,5) and spans over 50 kb of genomic DNA. It has a coding region of 3234 bp, which is contained within 6 exons (6).…”

Section: Structure Of the Calcium-sensing Receptormentioning

confidence: 99%

The calcium-sensing receptor and related diseases

D’Souza-Li

2006

Arq Bras Endocrinol Metab

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The calcium-sensing receptor (CASR) adjusts the extracellular calcium set point regulating PTH secretion and renal calcium excretion. The receptor is expressed in several tissues and is also involved in other cellular functions such as proliferation, differentiation and other hormonal secretion. High extracellular calcium levels activate the receptor resulting in modulation of several signaling pathways depending on the target tissues. Mutations in the CASR gene can result in gain or loss of receptor function. Gain of function mutations are associated to Autossomal dominant hypocalcemia and Bartter syndrome type V, while loss of function mutations are associated to Familial hypocalciuric hypercalcemia and Neonatal severe hyperparathyroidism. More than one hundred mutations were described in this gene. In addition to calcium, the receptor also interacts with several ions and polyamines. The CASR is a potential therapeutic target to treatment of diseases including hyperparathyroidism and osteoporosis, since its interaction with pharmacological compounds results in modulation of PTH secretion. RESUMO O Receptor Sensor de Cálcio e Doenças Associadas.O receptor sensor de cálcio (CASR) ajusta o set point do cálcio extracelular através da regulação da secreção de PTH e da excreção renal de cál-cio. O receptor é expresso em diversos tecidos e também está envolvido em outras funções celulares como proliferação, diferenciação e secreção de outros hormônios. Concentrações altas de cálcio extracelular ativam o receptor resultando em modulação de inúmeras vias de sinais intracelulares dependendo do tecido-alvo. Mutações no gene do CASR podem resultar em ganho ou perda de função do receptor. Mutações com ganho de função são associadas à Hipocalcemia autossômica dominante e à Síndrome de Bartter tipo V, enquanto que mutações com perda de função são associadas à Hipercalcemia hipocalciúrica familiar e ao Hiperparatireoidismo neonatal grave. Mais de cem mutações foram descritas neste gene. Além do cálcio, o receptor também interage com inúmeros íons e poliaminas. CASR é um alvo terapêutico potencial para tratamento de doenças incluindo hiperparatireoidismo e osteoporose, pois a sua interação com compostos farmacológicos resulta em modulação da secreção de PTH. [Ca 2+ o ] sensing mechanism that results in changes in phosphoinositide turnover and cytosolic calcium to regulate PTH secretion (1). Extracellular calcium regulates itself by serving as a first messenger and interacting with its receptor, the calcium-sensing receptor (CASR) on target tissues. The receptor was cloned in 1993 from bovine parathyroid (BoPCAR1) by expression cloning in Xenopus laevis oocytes and is a member of the G protein-coupled receptor super family (2). High calcium levels activate the CASR in the parathyroid cell surface to inhibit PTH secretion, and in the kidney to increase calcium excretion (3). STRUCTURE OF THE CALCIUM-SENSING RECEPTORThe human CASR gene is located on chromosome 3q13.3-21 (4,5) and spans over 50 kb of genomic DNA. It has...

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“…The human CASR gene is located on chromosome 3q13.3-21 (4,5) and spans over 50 kb of genomic DNA. It has a coding region of 3234 bp, which is contained within 6 exons (6).…”

Section: Structure Of the Calcium-sensing Receptormentioning

confidence: 99%

The calcium-sensing receptor and related diseases

D’Souza-Li

2006

Arq Bras Endocrinol Metab

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“…DNA was transferred to Nytran membranes (Schleicher & Schull, Inc., Keene, NH, USA), hybridized with the [ 32 P]-labeled 1618-base pair (bp) 1␣(OH)ase cDNA (Table 1) at 65°C, and washed under stringent conditions, all as described previously. (21) Gene linkage was determined by segregation analysis. (22) Gene order was determined by analyzing all hap- …”

Section: Interspecific Backcross Mice and Gene Mappingmentioning

confidence: 99%

25-Hydroxyvitamin D 1α-Hydroxylase: Structure of the Mouse Gene, Chromosomal Assignment, and Developmental Expression

Panda

Kawas

Seldin

et al. 2001

Journal of Bone and Mineral Research

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“…3-q21 (Janicic et al 1995). Exons 1A and 1B encode alternative 5 0 untranslated regions (5 0 -UTR) (Garrett et al 1995, Chikatsu et al 2000, exon 2 encodes the common 5 0 -UTR, the ATG initiation codon, the signal peptide sequence, and the beginning of the extracellular domain (ECD); exons 3-6 encode the main part of the ECD; and exon 7 encodes the end of the ECD, the transmembrane domain (TMD), and the intracellular domain (ICD).…”

Section: Introductionmentioning

confidence: 99%

Calcium-sensing receptor mutations and denaturing high performance liquid chromatography

Cole¹,

Yun²,

Wong³

et al. 2009

Journal of Molecular Endocrinology

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The calcium-sensing receptor (CASR), a plasma membrane G-protein-coupled receptor, is expressed in parathyroid gland and kidney, and controls systemic calcium homeostasis. Inactivating CASR mutations are associated with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism, and activating mutations cause autosomal dominant hypocalcemia (ADH). CASR mutation identification plays an important role in the clinical management of mineral metabolism disorders. We describe here a high-throughput method using screening with denaturing high performance liquid chromatography (DHPLC) to initially interrogate 12 amplicons covering translated exons and exon/intron boundaries, followed by sequencing of any amplicon with a modified melting curve relative to wild type, and direct sequencing of a 13th amplicon encoding the COOH-terminal tail to distinguish causative mutations from three common missense single nucleotide polymorphisms. A blinded analysis of 32 positive controls representing mutations throughout the CASR sequence, as well as 22 negative controls, yielded a concordance rate of 100%. We report eight novel and five recurrent FHH mutations, along with six novel and two recurrent ADH mutations. Thus, DHPLC provides a rapid and effective means to screen for CASR mutations.

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Mapping of the calcium-sensing receptor gene (CASR) to human Chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat Chromosome 11 and mouse Chromosome 16

Cited by 114 publications

References 27 publications

The calcium-sensing receptor and related diseases

The calcium-sensing receptor and related diseases

25-Hydroxyvitamin D 1α-Hydroxylase: Structure of the Mouse Gene, Chromosomal Assignment, and Developmental Expression

Calcium-sensing receptor mutations and denaturing high performance liquid chromatography

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