Abstract:
:Bone mineralization is an essential step during the embryonic development of vertebrates, and bone serves vital functions in human physiology. To systematically identify unique gene functions essential for osteogenesis, we performed a forward genetic screen in zebrafish and isolated a mutant, no bone (nob), that does not form any mineralized bone. Positional cloning of nob identified the causative gene to encode ectonucleoside triphosphate/diphosphohydrolase 5 (entpd5); analysis of its expression pattern demonstrates that entpd5 is specifically expressed in osteoblasts. An additional mutant, dragonfish (dgf), exhibits ectopic mineralization in the craniofacial and axial skeleton and encodes a loss-of-function allele of ectonucleotide pyrophosphatase phosphodiesterase 1 (enpp1). Intriguingly, generation of double-mutant nob/dgf embryos restored skeletal mineralization in nob mutants, indicating that mechanistically, Entpd5 and Enpp1 act as reciprocal regulators of phosphate/pyrophosphate homeostasis in vivo. Consistent with this, entpd5 mutant embryos can be rescued by high levels of inorganic phosphate, and phosphate-regulating factors, such as fgf23 and npt2a, are significantly affected in entpd5 mutant embryos. Our study demonstrates that Entpd5 represents a previously unappreciated essential player in phosphate homeostasis and skeletal mineralization.
journal_name
Proc Natl Acad Sci U S Aauthors
Huitema LF,Apschner A,Logister I,Spoorendonk KM,Bussmann J,Hammond CL,Schulte-Merker Sdoi
10.1073/pnas.1214231110subject
Has Abstractpub_date
2012-12-26 00:00:00pages
21372-7issue
52eissn
0027-8424issn
1091-6490pii
1214231110journal_volume
109pub_type
杂志文章abstract::Plasma norepinephrine and dopamine beta-hydroxylase (EC 1.14.17.1) activity were measured in rats. Adrenergic neuron blockade with bretylium for 4 hr and ganglion blockade with chlorisondamine for 72 hr lowered plasma norepinephrine. Neither treatment altered plasma dopamine beta-hydroxylase activity. Phenoxybenzamine...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Acanthamoeba castellanii contains two enzymes, myosins IA and IB, that exhibit the catalytic properties of a myosin but possess very unusual physical properties, the most striking of which are their single, low molecular weight heavy chain, their globular shape, and their inability to form bipolar filaments. We have n...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.83.13.4655
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abstract::Eukaryotic cells require N-linked carbohydrates for survival. However, the biosynthetic intermediate Man5GlcNAc2Asn, in place of mature N-linked structures, allows glycoprotein synthesis and somatic cell growth to proceed normally. To determine whether the same would be true in a complex biological situation, the gene...
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-01-04 00:00:00
abstract::Phospholipase Cε (PLCε) has been characterized as a direct effector of Ras in vitro and in cellular systems; however, the role of PLCε in tumorigenesis and its link to Ras in this context remain unclear. To assess the role of PLCε in Ras-driven cancers, we generated two new mouse strains: one carrying a targeted delet...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2014-03-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1998-11-10 00:00:00
abstract::We recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 88 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results sugg...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1988-01-01 00:00:00
abstract::Activating mutations in BRAF are found in 50% of melanomas and although treatment with BRAF inhibitors (BRAFi) is effective, resistance often develops. We now show that recently discovered NRAS isoform 2 is up-regulated in the setting of BRAF inhibitor resistance in melanoma, in both cell lines and patient tumor tissu...
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1988-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2003-08-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2020-04-07 00:00:00
abstract::Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host-derived cyclophili...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2020-12-22 00:00:00
abstract::Peroxiredoxins (Prx), a family of peroxidases that reduce intracellular peroxides with the thioredoxin system as the electron donor, are highly expressed in various cellular compartments. Among the antioxidant Prx enzymes, Prx2 is the most abundant in mammalian neurons, making it a prime candidate to defend against ox...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2007-11-20 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1982-04-01 00:00:00
abstract::The biotic recovery from Earth's most severe extinction event at the Permian-Triassic boundary largely reestablished the preextinction structure of marine trophic networks, with marine reptiles assuming the predator roles. However, the highest trophic level of today's marine ecosystems, i.e., macropredatory tetrapods ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
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更新日期:2013-01-22 00:00:00
abstract::We examined the MLL genomic translocation breakpoint in acute myeloid leukemia of infant twins. Southern blot analysis in both cases showed two identical MLL gene rearrangements indicating chromosomal translocation. The rearrangements were detectable in the second twin before signs of clinical disease and the intensit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.11.6413
更新日期:1998-05-26 00:00:00
abstract::The three members of the Brn-3 family of POU domain transcription factors are found in highly restricted sets of central nervous system neurons. Within the retina, these factors are present only within subsets of ganglion cells. We show here that in the developing mouse retina, Brn-3b protein is first observed in pres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.9.3920
更新日期:1996-04-30 00:00:00
abstract::A transcript generated by the distal part of the Duchenne Muscular Dystrophy (DMD) gene was initially detected in cells where the full size 14-kilobase (kb) messenger RNA is not found at a significant level. This transcript, approximately 4.5 kb long, corresponds to the cysteine-rich and carboxyl-terminal domains of d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.16.7506
更新日期:1992-08-15 00:00:00