Abstract:
:Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the calcium-sensing receptor (CaR) mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects of CaR deficiency on skeletal development and interactions between CaR and 1,25(OH)(2)D(3) or PTH on calcium and skeletal homeostasis, we compared the skeletal phenotypes of homozygous CaR-deficient (CaR(-/-)) mice to those of double homozygous CaR- and 1α(OH)ase-deficient [CaR(-/-)1α(OH)ase(-/-)] mice or those of double homozygous CaR- and PTH-deficient [CaR(-/-)PTH(-/-)] mice at 2 weeks of age. Compared to wild-type littermates, CaR(-/-) mice had hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth retardation. Chondrocyte proliferation and PTHrP expression in growth plates were reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin-positive areas, expression of the ALP, type I collagen, osteocalcin genes, and serum ALP levels were increased significantly. Deletion of 1α(OH)ase in CaR(-/-) mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus, greater elevation in PTH, slight improvement in skeletal growth with increased chondrocyte proliferation and PTHrP expression, and further increases in indices of osteoblastic bone formation. Deletion of PTH in CaR(-/-) mice resulted in rescue of early lethality, normocalcemia, increased serum phosphorus, undetectable serum PTH, normalization in skeletal growth with normal chondrocyte proliferation and enhanced PTHrP expression, and dramatic decreases in indices of osteoblastic bone formation. Our results indicate that reductions in hypercalcemia play a critical role in preventing the early lethality of CaR(-/-) mice and that defects in endochondral bone formation in CaR(-/-) mice result from effects of the marked elevation in serum calcium concentration and the decreases in serum phosphorus concentration and skeletal PTHrP levels, whereas the increased osteoblastic bone formation results from direct effects of PTH.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Liu J,Lv F,Sun W,Tao C,Ding G,Karaplis A,Brown E,Goltzman D,Miao Ddoi
10.1371/journal.pgen.1002294subject
Has Abstractpub_date
2011-09-01 00:00:00pages
e1002294issue
9eissn
1553-7390issn
1553-7404pii
PGENETICS-D-11-00733journal_volume
7pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Heterochromatic homology ensures the segregation of achiasmate chromosomes during meiosis I in Drosophila melanogaster females, perhaps as a consequence of the heterochromatic threads that connect achiasmate homologs during prometaphase I. Here, we ask how these threads, and other possible heterochromatic entanglement...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004650
更新日期:2014-10-23 00:00:00
abstract::In Drosophila, 50 classes of olfactory receptor neurons (ORNs) connect to 50 class-specific and uniquely positioned glomeruli in the antennal lobe. Despite the identification of cell surface receptors regulating axon guidance, how ORN axons sort to form 50 stereotypical glomeruli remains unclear. Here we show that the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007560
更新日期:2018-08-13 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pgen.1005038.]. ...
journal_title:PLoS genetics
pub_type: 已发布勘误
doi:10.1371/journal.pgen.1006559
更新日期:2017-01-20 00:00:00
abstract::Human chromosome 15q25 is involved in several disease-associated structural rearrangements, including microdeletions and chromosomal markers with inverted duplications. Using comparative fluorescence in situ hybridization, strand-sequencing, single-molecule, real-time sequencing and Bionano optical mapping analyses, w...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008075
更新日期:2019-03-27 00:00:00
abstract::The pentatricopeptide repeat (PPR) is a helical repeat motif found in an exceptionally large family of RNA-binding proteins that functions in mitochondrial and chloroplast gene expression. PPR proteins harbor between 2 and 30 repeats and typically bind single-stranded RNA in a sequence-specific fashion. However, the b...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002910
更新日期:2012-01-01 00:00:00
abstract::For many decades, Salmonella enterica has been subdivided by serological properties into serovars or further subdivided for epidemiological tracing by a variety of diagnostic tests with higher resolution. Recently, it has been proposed that so-called eBurst groups (eBGs) based on the alleles of seven housekeeping gene...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1007261
更新日期:2018-04-05 00:00:00
abstract::One of the crucial steps in endochondral bone formation is the replacement of a cartilage matrix produced by chondrocytes with bone trabeculae made by osteoblasts. However, the precise sources of osteoblasts responsible for trabecular bone formation have not been fully defined. To investigate whether cells derived fro...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004820
更新日期:2014-12-04 00:00:00
abstract::Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controlling CO localization are not well understood. We previously showed that mei...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008894
更新日期:2020-06-29 00:00:00
abstract::Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause re...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004465
更新日期:2014-06-26 00:00:00
abstract::Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast B(act) spliceosomes formed on site-specifically labeled pre-mRNA,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005539
更新日期:2015-09-22 00:00:00
abstract::Maintaining levels of calcium in the cytosol is important for many cellular events, including cell migration, where localized regions of high calcium are required to regulate cytoskeletal dynamics, contractility, and adhesion. Studies show inositol-trisphosphate receptors (IP3R) and ryanodine receptors (RyR), which re...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003506
更新日期:2013-05-01 00:00:00
abstract::Efficient adaptation to iron starvation is an essential virulence determinant of the most common human mold pathogen, Aspergillus fumigatus. Here, we demonstrate that the cytosolic monothiol glutaredoxin GrxD plays an essential role in iron sensing in this fungus. Our studies revealed that (i) GrxD is essential for gr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008379
更新日期:2019-09-16 00:00:00
abstract::Association mapping is a powerful approach for dissecting the genetic architecture of complex quantitative traits using high-density SNP markers in maize. Here, we expanded our association panel size from 368 to 513 inbred lines with 0.5 million high quality SNPs using a two-step data-imputation method which combines ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004573
更新日期:2014-09-11 00:00:00
abstract::Massively parallel pyrosequencing of hypervariable regions from small subunit ribosomal RNA (SSU rRNA) genes can sample a microbial community two or three orders of magnitude more deeply per dollar and per hour than capillary sequencing of full-length SSU rRNA. As with full-length rRNA surveys, each sequence read is a...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000255
更新日期:2008-11-01 00:00:00
abstract::Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea th...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000599
更新日期:2009-08-01 00:00:00
abstract::Genome-wide association studies (GWAS) have identified >500 common variants associated with quantitative metabolic traits, but in aggregate such variants explain at most 20-30% of the heritable component of population variation in these traits. To further investigate the impact of genotypic variation on metabolic trai...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004147
更新日期:2014-01-30 00:00:00
abstract::Most of the somatic cells of adult metazoans, including mammals, do not undergo continuous cycles of replication. Instead, they are quiescent and devote most of their metabolic activity to gene expression. The mutagenic consequences of exposure to DNA-damaging agents are well documented, but less is known about the im...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000577
更新日期:2009-07-01 00:00:00
abstract::Aging in Caenorhabditis elegans is characterized by widespread physiological and molecular changes, but the mechanisms that determine the rate at which these changes occur are not well understood. In this study, we identify a novel link between reproductive aging and somatic aging in C. elegans. By measuring global ag...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005725
更新日期:2015-12-11 00:00:00
abstract::Mutational fitness effects can be measured with relatively high accuracy in viruses due to their small genome size, which facilitates full-length sequencing and genetic manipulation. Previous work has shown that animal and plant RNA viruses are very sensitive to mutation. Here, we characterize mutational fitness effec...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000742
更新日期:2009-11-01 00:00:00
abstract::Vegetative phase change is regulated by a decrease in the abundance of the miRNAs, miR156 and miR157, and the resulting increase in the expression of their targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors. To determine how miR156/miR157 specify the quantitative and qualitative changes in lea...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007337
更新日期:2018-04-19 00:00:00
abstract::Nonallelic homologous recombination (NAHR) between highly similar duplicated sequences generates chromosomal deletions, duplications and inversions, which can cause diverse genetic disorders. Little is known about interindividual variation in NAHR rates and the factors that influence this. We estimated the rate of del...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004195
更新日期:2014-03-06 00:00:00
abstract::Lifespan can be extended by reduction of dietary intake. This practice is referred to as dietary restriction (DR), and extension of lifespan by DR is evolutionarily conserved in taxonomically diverse organisms including yeast, invertebrates, and mammals. Although these two often-stated facts carry the implication that...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.0030057
更新日期:2007-04-27 00:00:00
abstract::Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES) cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and ide...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030145
更新日期:2007-08-01 00:00:00
abstract::Topoisomerase 3α, a class I topoisomerase, consists of a TOPRIM domain, an active centre and a variable number of zinc-finger domains (ZFDs) at the C-terminus, in multicellular organisms. Whereas the functions of the TOPRIM domain and the active centre are known, the specific role of the ZFDs is still obscure. In cont...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007674
更新日期:2018-09-17 00:00:00
abstract::Gene retroposition leads to considerable genetic variation between individuals. Recent studies revealed the presence of at least 208 retroduplication variations (RDVs), a class of polymorphisms, in which a retrocopy is present or absent from individual genomes. Most of these RDVs resulted from recent retroduplications...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005579
更新日期:2015-10-16 00:00:00
abstract::Calpains constitute a superfamily of Ca2+-dependent cysteine proteases, indispensable for various cellular processes. Among the 15 mammalian calpains, calpain 8/nCL-2 and calpain 9/nCL-4 are predominantly expressed in the gastrointestinal tract and are restricted to the gastric surface mucus (pit) cells in the stomach...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001040
更新日期:2010-07-29 00:00:00
abstract::A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biolo...
journal_title:PLoS genetics
pub_type: 杂志文章,随机对照试验
doi:10.1371/journal.pgen.1004818
更新日期:2014-12-04 00:00:00
abstract::Microtubule-microfilament interactions are important for cytokinesis and subcellular localization of proteins and mRNAs. In the early zebrafish embryo, astral microtubule-microfilament interactions also facilitate a stereotypic segregation pattern of germ plasm ribonucleoparticles (GP RNPs), which is critical for thei...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003448
更新日期:2013-04-01 00:00:00
abstract::Type-III protein secretion systems are utilized by gram-negative pathogens to secrete building blocks of the bacterial flagellum, virulence effectors from the cytoplasm into host cells, and structural subunits of the needle complex. The flagellar type-III secretion apparatus utilizes both the energy of the proton moti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004800
更新日期:2014-11-13 00:00:00
abstract::The deluge of data generated by genome sequencing has led to an increasing reliance on bioinformatic predictions, since the traditional experimental approach of characterizing gene function one at a time cannot possibly keep pace with the sequence-based discovery of novel genes. We have utilized Biolog phenotype Micro...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000211
更新日期:2008-10-03 00:00:00