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1.
J Fish Biol ; 85(3): 597-604, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24976249

ABSTRACT

Individual zebrafish Danio rerio were assayed for exploratory tendency in a serial open field test before and after being maintained on one of four diet treatments that differed in ration and in predictability of food delivery. Danio rerio became more exploratory after being maintained on a diet with a predictable delivery schedule. There was no effect of ration. Thus, exploratory behaviour is inducible by environmental influences independent of genetic predisposition or social interactions. These results have implications for management of correlated behavioural syndromes of exploratory and boldness of animals reared in captivity for later release into wild populations.


Subject(s)
Behavior, Animal , Diet , Exploratory Behavior , Zebrafish/physiology , Animals , Feeding Behavior
2.
Clin Exp Immunol ; 172(1): 63-72, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23480186

ABSTRACT

Splenectomy has been used in patients with common variable immunodeficiency disorders (CVID), mainly in the context of refractory autoimmune cytopenia and suspected lymphoma, but there are understandable concerns about the potential of compounding an existing immunodeficiency. With increasing use of rituximab as an alternative treatment for refractory autoimmune cytopenia, the role of splenectomy in CVID needs to be re-examined. This retrospective study provides the largest cohesive data set to date describing the outcome of splenectomy in 45 CVID patients in the past 40 years. Splenectomy proved to be an effective long-term treatment in 75% of CVID patients with autoimmune cytopenia, even in some cases when rituximab had failed. Splenectomy does not worsen mortality in CVID and adequate immunoglobulin replacement therapy appears to play a protective role in overwhelming post-splenectomy infections. Future trials comparing the effectiveness and safety of rituximab and splenectomy are needed to provide clearer guidance on the second-line management of autoimmune cytopenia in CVID.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Common Variable Immunodeficiency/therapy , Immunoglobulins/therapeutic use , Immunologic Factors/therapeutic use , Adolescent , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/pharmacology , Child , Common Variable Immunodeficiency/immunology , Common Variable Immunodeficiency/mortality , Common Variable Immunodeficiency/surgery , Disease Management , Female , Humans , Immunoglobulins/pharmacology , Immunologic Factors/pharmacology , Male , Middle Aged , Retrospective Studies , Rituximab , Splenectomy , Survival Rate , Treatment Outcome
3.
Hum Mol Genet ; 18(11): 1909-23, 2009 Jun 01.
Article in English | MEDLINE | ID: mdl-19279158

ABSTRACT

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7(Gt/+) olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development.


Subject(s)
Abnormalities, Multiple/physiopathology , Cell Proliferation , DNA Helicases/genetics , DNA-Binding Proteins/genetics , Olfaction Disorders/physiopathology , Sensory Receptor Cells/cytology , Stem Cells/cytology , Abnormalities, Multiple/genetics , Abnormalities, Multiple/metabolism , Animals , Child , DNA Helicases/metabolism , DNA-Binding Proteins/metabolism , Disease Models, Animal , Female , Gene Expression , Humans , Male , Mice , Mice, Knockout , Mutation , Olfaction Disorders/genetics , Olfaction Disorders/metabolism , Olfactory Mucosa/cytology , Olfactory Mucosa/growth & development , Olfactory Mucosa/metabolism , Sensory Receptor Cells/metabolism , Smell , Stem Cells/metabolism
4.
Plant Dis ; 92(7): 1062-1066, 2008 Jul.
Article in English | MEDLINE | ID: mdl-30769533

ABSTRACT

Phytophthora root rot, caused by Phytophthora sojae, is the most important disease of soybean (Glycine max) in North Dakota. Because of the expansion of soybean hectares and appearance of disease on cultivars with resistance genes, we investigated the pathotypes, distribution, and metalaxyl sensitivity of P. sojae in North Dakota. Soil from 347 soybean fields in 20 counties in eastern North Dakota was collected between 2002 and 2004, and P. sojae was baited from the soil with the susceptible cultivar McCall. The virulence phenotype of each isolate was determined on eight differentials, and all isolates were tested for sensitivity to metalaxyl incorporated into V8 agar. The pathogen was recovered from 80 fields located in five counties. Sixteen pathotypes, which included 14 known races and two previously reported pathotypes that had not been assigned a race, were identified out of 157 isolates. A single pathotype was recovered from 61 fields, 2 pathotypes from 14 fields, 3 pathotypes from 4 fields, and 4 pathotypes from 1 field. Pathotypes with virulence phenotypes 1a,1c,7 (race 4; 39%) and 1a,7 (race 3; 28%) were the most common, representing 67% of the total isolates. One or both of these pathotypes was found in 79% of the fields where P. sojae was recovered. Seven of the 157 isolates showed limited growth on metalaxyl after 14 days of incubation. In the past 10 years, the number of pathotypes of P. sojae in North Dakota has increased from 4 to 16, and pathotypes have developed that can attack the three most common resistance genes found in soybean cultivars for the region.

5.
J Neurosci ; 24(44): 10022-34, 2004 Nov 03.
Article in English | MEDLINE | ID: mdl-15525788

ABSTRACT

A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel alpha subunit. The mutation decreased modulation of the alpha subunit by beta1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of beta1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type alpha subunit with the beta1 or beta3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for beta subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the alpha and beta1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility.


Subject(s)
Epilepsy, Generalized/genetics , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/physiology , Sodium Channels/genetics , Sodium Channels/physiology , Action Potentials/genetics , Action Potentials/physiology , Amino Acid Sequence , Animals , Cricetinae , Cricetulus , Cytoplasm , Epilepsy, Generalized/complications , Epilepsy, Generalized/physiopathology , Female , Humans , Ion Channel Gating/genetics , Ion Channel Gating/physiology , Kinetics , Male , Models, Neurological , Molecular Sequence Data , Mutation , NAV1.1 Voltage-Gated Sodium Channel , Neurons/physiology , Oocytes , Protein Structure, Tertiary , Recombinant Proteins , Saccharomyces cerevisiae , Seizures, Febrile/complications , Seizures, Febrile/genetics , Seizures, Febrile/physiopathology , Voltage-Gated Sodium Channel beta-1 Subunit , Xenopus laevis
6.
Water Sci Technol ; 50(4): 9-16, 2004.
Article in English | MEDLINE | ID: mdl-15484737

ABSTRACT

Biosolids odour emissions can affect the ability of wastewater utilities to implement beneficial biosolids processing and reuse programs. Communities often become more sensitised and vocal about biosolids issues, once they experience odours emanating from a nearby site. Odour impacts from biosolids, including potential human health effects, have been targeted recently by many national and local newspapers, citizens' groups, and regulatory agencies, who have raised significant concerns, ranging from viable disposal methods/sites to outright bans. Many national and local regulatory agencies in the United States are considering biosolids disposal bans in their communities because of misinformation, poor science, and citizen pressure, but primarily because of odour impact concerns. The wastewater industry has a relatively poor understanding of the operations and treatment parameters that influence biosolids odour emissions. Thus, wastewater treatment plants are often unable to control the odour quality of the biosolids that are delivered into communities. A research study to demonstrate the influence of anaerobic digestion, mechanical dewatering, and storage design and operating parameters on the odour quality of the final product was performed and is the subject of this paper. Established and new sampling and analytical methods were used to measure biosolids odour emissions from 11 test sites in North America. By determining the impacts of these control variables on biosolids odour quality, design and operations of anaerobic digestion systems might be enhanced. This paper also summarises a corollary study performed as part of the WERF research study that addresses the health effects of biosolids odours.


Subject(s)
Odorants/analysis , Odorants/prevention & control , Public Health , Waste Disposal, Fluid/methods , Community Participation , Environmental Monitoring/statistics & numerical data , Public Opinion , Public Policy , Quality Control , United States
7.
Nat Cell Biol ; 3(10): 933-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11584277

ABSTRACT

Proper positioning of mitotic spindles ensures equal allocation of chromosomes to daughter cells. This often involves interactions between spindle and astral microtubules and cortical actin. In yeast and Caenorhabditis elegans, some of the protein machinery that connects spindles and cortex has been identified but, in most animal cells, this process remains mysterious. Here, we report that the tumour suppressor homologue APC2 and its binding partner Armadillo both play roles in spindle anchoring during the syncytial mitoses of early Drosophila embryos. Armadillo, alpha-catenin and APC2 all localize to sites of cortical spindle attachment. APC2-Armadillo complexes often localize with interphase microtubules. Zeste-white 3 kinase, which can phosphorylate Armadillo and APC, is also crucial for spindle positioning and regulates the localization of APC2-Armadillo complexes. Together, these data suggest that APC2, Armadillo and alpha-catenin provide an important link between spindles and cortical actin, and that this link is regulated by Zeste-white 3 kinase.


Subject(s)
Actins/metabolism , Cytoskeletal Proteins/metabolism , Drosophila Proteins , Drosophila melanogaster/embryology , Glycogen Synthase Kinase 3 , Insect Proteins/metabolism , Spindle Apparatus/metabolism , Trans-Activators , Animals , Armadillo Domain Proteins , Cadherins/metabolism , Cytoskeletal Proteins/genetics , Drosophila melanogaster/cytology , Drosophila melanogaster/genetics , Giant Cells/metabolism , Humans , Microscopy, Fluorescence , Mitosis , Protein Serine-Threonine Kinases/metabolism , Spindle Apparatus/ultrastructure , Transcription Factors , alpha Catenin
8.
J Neurosci ; 21(19): 7517-25, 2001 Oct 01.
Article in English | MEDLINE | ID: mdl-11567041

ABSTRACT

Contactin (also known as F3, F11) is a surface glycoprotein that has significant homology with the beta2 subunit of voltage-gated Na(+) channels. Contactin and Na(+) channels can be reciprocally coimmunoprecipitated from brain homogenates, indicating association within a complex. Cells cotransfected with Na(+) channel Na(v)1.2alpha and beta1 subunits and contactin have threefold to fourfold higher peak Na(+) currents than cells with Na(v)1.2alpha alone, Na(v)1.2/beta1, Na(v)1.2/contactin, or Na(v)1.2/beta1/beta2. These cells also have a correspondingly higher saxitoxin binding, suggesting an increased Na(+) channel surface membrane density. Coimmunoprecipitation of different subunits from cell lines shows that contactin interacts specifically with the beta1 subunit. In the PNS, immunocytochemical studies show a transient colocalization of contactin and Na(+) channels at new nodes of Ranvier forming during remyelination. In the CNS, there is a particularly high level of colocalization of Na(+) channels and contactin at nodes both during development and in the adult. Contactin may thus significantly influence the functional expression and distribution of Na(+) channels in neurons.


Subject(s)
Cell Adhesion Molecules, Neuronal/metabolism , Sodium Channels/metabolism , Animals , Axons/metabolism , Axons/pathology , Binding, Competitive/drug effects , Brain Chemistry , CHO Cells , Cell Adhesion Molecules, Neuronal/genetics , Cell Line , Cell Membrane/chemistry , Cell Membrane/metabolism , Contactins , Cricetinae , Demyelinating Diseases/chemically induced , Demyelinating Diseases/pathology , Female , Gene Expression , Lysophosphatidylcholines/pharmacology , NAV1.2 Voltage-Gated Sodium Channel , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Patch-Clamp Techniques , Precipitin Tests , Protein Subunits , Ranvier's Nodes/metabolism , Rats , Saxitoxin/metabolism , Saxitoxin/pharmacokinetics , Sciatic Nerve/drug effects , Sciatic Nerve/pathology , Sodium/metabolism , Sodium Channel Blockers , Sodium Channels/genetics , Tetrodotoxin/pharmacology , Transfection
9.
Curr Biol ; 11(13): R524-6, 2001 Jul 10.
Article in English | MEDLINE | ID: mdl-11470426

ABSTRACT

Frizzled receptors can activate two alternative signal transduction pathways: the canonical Wnt pathway or the planar cell polarity pathway. Recent studies of the Naked cuticle protein suggest a mechanism for the inactivation of the canonical pathway and concomitant activation of the planar cell polarity pathway.


Subject(s)
Drosophila Proteins , Insect Proteins/physiology , Proto-Oncogene Proteins/antagonists & inhibitors , Signal Transduction , Zebrafish Proteins , Animals , Body Patterning , Models, Biological , Proto-Oncogene Proteins/physiology , Wnt Proteins
10.
Anal Biochem ; 291(1): 109-17, 2001 Apr 01.
Article in English | MEDLINE | ID: mdl-11262163

ABSTRACT

Three BODIPY GTPgammaS analogs (FL, 515, and TR), BODIPY FL GppNHp and BODIPY FL GTP molecules were synthesized as possible fluorescent probes to study guanine nucleotide binding spectroscopically. Binding to G(alphao) increases baseline analog fluorescence by 6-, 8.5-, 2.8-, 3.5-, and 3.0-fold, respectively. Binding of GTPgammaS and GppNHp analogs to G(alphao) is of high affinity (K(D) 11, 17, 55, and 110 nM, respectively) and reaches a stable plateau while fluorescence of BODIPY FL GTP shows a transient increase which returns to baseline. Furthermore, BODIPY FL GTPgammaS shows varying affinities for alpha(o), alpha(s), alpha(i1), and alpha(i2) (6, 58, 150, and 300 nM). The affinities of BODIPY FL GppNHp for all four G(alpha) subunits are 10-fold lower than for BODIPY FL GTPgammaS. Half-times for the fluorescence increase are consistent with known GDP release rates for those proteins. Enhancement of fluorescence upon binding the G(alpha) subunit is most likely due to a rotation around the gamma-thiol (GTPgammaS) or the 3' ribose-hydroxyl (GppNHp) bond to relieve the quenching of BODIPY fluorescence by the guanine base. Binding to G(alpha) exposes the BODIPY moiety to the external environment, as seen by an increase in sodium iodide quenching. The visible excitation and emission spectra and high fluorescence levels of these probes permit robust real-time detection of nucleotide binding.


Subject(s)
Boron Compounds/chemical synthesis , Fluorescent Dyes/chemistry , GTP-Binding Proteins/chemistry , Guanosine Triphosphate/analogs & derivatives , Guanosine Triphosphate/chemistry , Escherichia coli , GTP-Binding Proteins/metabolism , Guanosine Diphosphate/chemistry , Protein Binding , RGS Proteins/metabolism
11.
Semin Perioper Nurs ; 10(1): 17-23, 2001 Jan.
Article in English | MEDLINE | ID: mdl-15129501

ABSTRACT

Benign prostatic hypertrophy (BPH) is a medical condition causing obstructive urinary symptoms that will inevitably affect the majority of the male population. Treatments for BPH have traditionally included invasive surgical intervention to resect a portion of the prostate as a relief of obstructive symptoms or medications that act in several ways to open the urinary channel and relieve symptoms. A new, less invasive treatment for BPH has now been developed and approved. Transurethral microwave therapy is discussed in this article. A case study is presented.


Subject(s)
Diathermy/methods , Microwaves/therapeutic use , Prostatic Hyperplasia/therapy , Aged , Diathermy/nursing , Humans , Male , Patient Education as Topic/methods , Perioperative Care/methods , Perioperative Care/nursing , Perioperative Nursing/methods , Prostatic Hyperplasia/diagnosis , Treatment Outcome
12.
Genetics ; 155(4): 1725-40, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10924470

ABSTRACT

During development signaling pathways coordinate cell fates and regulate the choice between cell survival or programmed cell death. The well-conserved Wingless/Wnt pathway is required for many developmental decisions in all animals. One transducer of the Wingless/Wnt signal is Armadillo/beta-catenin. Drosophila Armadillo not only transduces Wingless signal, but also acts in cell-cell adhesion via its role in the epithelial adherens junction. While many components of both the Wingless/Wnt signaling pathway and adherens junctions are known, both processes are complex, suggesting that unknown components influence signaling and junctions. We carried out a genetic modifier screen to identify some of these components by screening for mutations that can suppress the armadillo mutant phenotype. We identified 12 regions of the genome that have this property. From these regions and from additional candidate genes tested we identified four genes that suppress arm: dTCF, puckered, head involution defective (hid), and Dpresenilin. We further investigated the interaction with hid, a known regulator of programmed cell death. Our data suggest that Wg signaling modulates Hid activity and that Hid regulates programmed cell death in a dose-sensitive fashion.


Subject(s)
Cytoskeletal Proteins/genetics , Drosophila Proteins , Drosophila/genetics , Insect Proteins/genetics , Suppression, Genetic , Trans-Activators , Animals , Apoptosis/genetics , Armadillo Domain Proteins , Cell Division/genetics , Chromosomes , Crosses, Genetic , Histones/metabolism , In Situ Nick-End Labeling , Insect Proteins/physiology , Models, Genetic , Neuropeptides/genetics , Neuropeptides/physiology , Phalloidine/metabolism , Phenotype , Proto-Oncogene Proteins/genetics , Transcription Factors , Wnt1 Protein , beta Catenin
14.
Development ; 127(16): 3607-17, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10903184

ABSTRACT

Elaboration of the Drosophila body plan depends on a series of cell-identity decisions and morphogenetic movements regulated by intercellular signals. For example, Jun N-terminal kinase signaling regulates cell fate decisions and morphogenesis during dorsal closure, while Wingless signaling regulates segmental patterning of the larval cuticle via Armadillo. wingless or armadillo mutant embryos secrete a lawn of ventral denticles; armadillo mutants also exhibit dorsal closure defects. We found that mutations in puckered, a phosphatase that antagonizes Jun N-terminal kinase, suppress in a dose-sensitive manner both the dorsal and ventral armadillo cuticle defects. Furthermore, we found that activation of the Jun N-terminal kinase signaling pathway suppresses armadillo-associated defects. Jun N-terminal kinase signaling promotes dorsal closure, in part, by regulating decapentaplegic expression in the dorsal epidermis. We demonstrate that Wingless signaling is also required to activate decapentaplegic expression and to coordinate cell shape changes during dorsal closure. Together, these results demonstrate that MAP-Kinase and Wingless signaling cooperate in both the dorsal and ventral epidermis, and suggest that Wingless may activate both the Wingless and the Jun N-terminal kinase signaling cascades.


Subject(s)
Body Patterning/physiology , Drosophila Proteins , Drosophila/embryology , Mitogen-Activated Protein Kinase Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Signal Transduction/physiology , Trans-Activators , Animals , Armadillo Domain Proteins , Drosophila/genetics , Drosophila/physiology , Enzyme Activation , Insect Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/physiology , Mitogen-Activated Protein Kinase Kinases/genetics , Mutagenesis , Phosphoprotein Phosphatases/genetics , Phosphoprotein Phosphatases/physiology , Proto-Oncogene Proteins/genetics , Transcription Factors , Wnt1 Protein
15.
Mech Dev ; 90(2): 283-7, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10640713

ABSTRACT

Fibroblast growth factors (FGFs) 11-14 comprise a subfamily of FGFs with poorly defined biological function. Here we characterize two isoforms of FGF14 (FGF14-1a and FGF14-1b) that result from the alternative usage of two different first exons. We demonstrate that these isoforms have differential subcellular localization and that they are differentially expressed in various adult tissues. Using in situ hybridization we show that Fgf14 is widely expressed in brain, spinal cord, major arteries and thymus between 12.5 and 14.5 days of mouse embryonic development. We also show that during cerebellar development, Fgf14 is first observed at postnatal day 1 in post mitotic granule cells, and later in development, in migrating and post migratory granule cells. The developmental expression pattern of Fgf14 in the cerebellum is complementary to that of Math1, a marker for proliferating granule cells in the external germinal layer.


Subject(s)
Alternative Splicing , Fibroblast Growth Factors/genetics , Gene Expression Regulation, Developmental , 3T3 Cells , Amino Acid Sequence , Animals , Mice , Molecular Sequence Data , Protein Isoforms/genetics , Sequence Homology, Amino Acid , Subcellular Fractions
17.
Semin Perioper Nurs ; 9(4): 168-72, 2000 Oct.
Article in English | MEDLINE | ID: mdl-12029771

ABSTRACT

This article reviews the definition of acoustic neuroma, prevalence, growth, symptoms, diagnosis, multiple treatment options, postoperative complications, alternative therapies, and patient and health care provider resources.


Subject(s)
Neuroma, Acoustic , Humans , Neuroma, Acoustic/diagnosis , Neuroma, Acoustic/physiopathology , Neuroma, Acoustic/surgery , Postoperative Care
18.
J Biol Chem ; 274(43): 30934-42, 1999 Oct 22.
Article in English | MEDLINE | ID: mdl-10521488

ABSTRACT

Signaling through fibroblast growth factor receptors (FGFRs) is critical for the development and patterning of the vertebrate skeleton. Gain-of-function alleles of fgfr2 and fgfr3 have been linked to several dominant skeletal disorders in humans, while null mutations in fgfr3 result in the overgrowth of long bones in a mouse model system. Interestingly, the expression pattern of fgfr3 in growth plate chondrocytes overlaps that of the parathyroid hormone (PTH)-related peptide (PTHrP) receptor, a signaling molecule that also regulates endochondral ossification. The coincident expression of these two receptors suggests that their signaling pathways may also interact. To gain insight into the regulatory mechanism(s) that govern the expression of the fgfr3 gene in chondrocytes, we have identified a cell-specific transcriptional regulatory element (CSRh) by measuring the activity of various promoter fragments in FGFR3-expressing (CFK2) and nonexpressing (RCJ) chondrocyte-like cell lines. Furthermore, we demonstrate that activation of PTH/PTHrP receptors, either by stimulation with PTH or through the introduction of activating mutations, represses CSRh-mediated transcriptional activity. Finally, the transcriptional repression of the CSRh element was mimicked by treatment with forskolin, 8-bromo-cAMP, and 3-isobutyl-1-methylxanthine or by overexpression of the catalytic subunit of protein kinase A. Together, these data suggest that protein kinase A activity is a critical factor that regulates fgfr3 gene expression in the proliferative or prehypertrophic compartment of the epiphyseal growth plate. Furthermore, these results provide a possible link between PTHrP signaling and fgfr3 gene expression during the process of endochondral ossification.


Subject(s)
1-Methyl-3-isobutylxanthine/pharmacology , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Cyclic AMP/metabolism , Gene Expression Regulation/physiology , Growth Plate/metabolism , Protein-Tyrosine Kinases , Receptors, Fibroblast Growth Factor/genetics , Receptors, Parathyroid Hormone/genetics , Regulatory Sequences, Nucleic Acid , Transcription, Genetic , Animals , Base Sequence , Cell Line , Cyclic AMP Response Element-Binding Protein/metabolism , Gene Expression Regulation/drug effects , Humans , Kinetics , Mice , Molecular Sequence Data , Mutagenesis, Site-Directed , Oligodeoxyribonucleotides/chemistry , Oligodeoxyribonucleotides/metabolism , Parathyroid Hormone/pharmacology , Promoter Regions, Genetic , Receptor, Fibroblast Growth Factor, Type 3 , Receptor, Parathyroid Hormone, Type 1 , Recombinant Proteins/biosynthesis , Transcription, Genetic/drug effects , Transfection
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