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公开(公告)号：US20080200414A1
公开(公告)日：2008-08-21
申请号：US11938894
申请日：2007-11-13
摘要： Novel nucleic acids and corresponding encoded proteins are described. Also described are corresponding recombinant vectors and host cells, as well as methods of producing the proteins. Also described are mimetics and antibodies to the proteins as well as compositions comprising the nucleic acid or proteins or a portion thereof. Methods and kits for the detection of a disease, disorder or abnormal physical state caused by abnormal modulation of calcium levels in a patient are also described. Methods for treating a patient having a disease, disorder or abnormal physical state caused by abnormal calcium levels are also described. Methods for assaying abnormal calcium levels are also described, as are methods for screening the efficacy of products for modulating abnormal calcium levels.
摘要翻译： 描述了新的核酸和相应的编码的蛋白质。 还描述了相应的重组载体和宿主细胞，以及产生蛋白质的方法。 还描述了模拟物和蛋白质的抗体以及包含核酸或蛋白质或其一部分的组合物。 还描述了用于检测由患者中钙水平的异常调节引起的疾病，病症或异常身体状态的方法和试剂盒。 还描述了治疗由异常钙水平引起的疾病，病症或异常身体状况的患者的方法。 还描述了测定异常钙水平的方法，以及用于筛选产物用于调节异常钙水平的功效的方法。
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公开(公告)号：US20050181442A1
公开(公告)日：2005-08-18
申请号：US11108784
申请日：2005-04-19
摘要： This invention relates to a novel gene that shows tissue specific expression and increased expression in a low calcium concentration medium. Low renin hypertension is characterized by decreased levels of serum ionized calcium in the presence of increased levels of parathyroid hormone. It is hypothesized that hypertensive factor(s) are co-secreted with PTH in SHR, a model of low renin hypertension, the parathyroid hypertensive factor being one of them. As a negative calcium balance is present in spontaneously hypertensive rats (SHR), we searched for gene(s) involved in this dysregulation. A cDNA library was constructed from the SHR parathyroid gland which is a key regulator of serum ionized calcium. From 7 overlapping DNA fragments, a 1100-bp novel cDNA containing an open reading frame of 224 codons was reconstituted. This novel gene, named HCaRG (Hypertension-related, Calcium-regulated Gene), was negatively regulated by extracellular calcium concentration and its basal mRNA levels were higher in hypertensive animals. The deduced protein showed no transmembrane domain, 67% a helix content, a mutated calcium-binding site (EF-hand motif), 4 putative ‘leucine zipper’ motifs and a nuclear receptor-binding domain. At the subcellular level, HCaRG had a nuclear localization. We cloned the human homolog of this gene. Sequence comparison revealed 80% homology between rats and humans at the nucleotide and amino acid sequences. Tissue distribution showed a preponderance in the heart, stomach, jejunum, kidney (tubular fraction), liver and adrenal gland (mainly in the medulla). HCaRG mRNA was significantly more expressed in adult than in fetal organs, and its levels were decreased in tumors and cancerous cell lines. We observed that after 60-min ischemia followed by reperfusion, HCaRG mRNA declined rapidly in contrast with an increase in c-myc mRNA. Its levels then rose steadily to exceed baseline at 48 h of reperfusion. HEK293 cells stably transfected with HCaRG exhibited much lower proliferation, as shown by cell count and 3 H-thymidine incorporation. Taken together, our results suggest that HCaRG is a nuclear protein potentially involved in the control of cell proliferation.
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