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Biomedical subjects

Q Wang

Publications and source records attributed to Q Wang.

At least 199 records · Page 11Linked to original sources
PubMed2001

Detection of occult metastatic lymph nodes in the neck with gray-scale and power Doppler US.

PURPOSE: To determine the most accurate criterion for predicting malignancy of small cervical lymph nodes with gray-scale ultrasound (GSUS) and power Doppler ultrasound (PDUS). MATERIAL AND METHODS: Findings of 69 pathologically verified cervical nodes (38 benign, 31 malignant) in 57 patients without wide echogenic hilum on GSUS that measured less than 10 mm in minimal axial diameter were prospectively studied. Minimal and maximal axial diameters, ratios of minimal to maximal axial diameters, and presence or absence of calcification or necrosis of the nodes were assessed. On PDUS, vascularity in the node was classified into 4 pattern groups. A logistic model was used to evaluate the significant factors for predicting malignancy. RESULTS: The logistic model revealed that the minimal axial diameter and vascularity patterns were the only significant factors for malignancy. Using the minimal axial diameter, a node larger than 8 mm showed the highest accuracy (73%) with 45% sensitivity and 93% specificity. Of the vascularity patterns, spotted or peripheral pattern had the highest accuracy (80%) with 61% sensitivity and 93% specificity. A combined criterion of the minimal axial diameter larger than 8 mm and spotted or peripheral pattern increased the accuracy to 82% and sensitivity to 77% but specificity decreased to 86%. CONCLUSION: A combined criterion of minimal axial diameter and vascular patterns was most accurate for diagnosing occult metastatic lymph nodes in the neck.

Adult↗
PubMed2001

Enhancement of dewaterability of thickened waste activated sludge by freezing and thawing treatment.

The effect of freezing speed on dewaterability of waste activated sludge thickened by flotation was investigated. The average dewatering rate of the sludge after freezing/thawing treatment was remarkably increased, and was found to be larger in the order: slow-frozen (-10 degrees C, -20 degrees C) > fast-frozen (-80 degrees C) > unfrozen sludge. This order was consistent with those of the sludge settling, elution of intracellular water and the numbers of the viable bacteria in the sludges after freezing/thawing. The expression characteristics and the final moisture contents of unfrozen and frozen sludge were evaluated from expession experiments at constant pressure. The wet-basis moisture content of final cake of frozen sludge was about 10% lower than those of unfrozen sludge, and even the cake obtained under additional 2 kgf/cm2 pressure may burn without auxiliary fuel. In addition, the mechanism responsible for the sludge dewatering was also examined.

Freezing↗
PubMed2001

Hepatopoietin acts as an autocrine growth factor in hepatoma cells.

Hepatopoietin (HPO) is a novel human hepatotrophic factor. Its known function is mainly limited to supporting liver regeneration. Recently, it was shown by our laboratory that HPO acts as a mitogen for hepatoma cell lines and that there are HPO-specific receptors on the surface of these cells (Wang, G., et al., J Biol Chem 1999;274:11469-11472), indicating that HPO might be involved in oncogenesis in the liver. To study this hypothesis, we first conducted experiments in vitro to identify the existence of an autocrine loop of HPO/HPO receptor in hepatoma cell lines. It was demonstrated that HPO was actually expressed by hepatoma cells, such as HepG2, Bel 7402, and SMMC-7721, and secreted into the culture medium. Furthermore, it was shown that HPO-neutralizing antibody has an inhibitory effect on the uptake of tritiated thymidine by hepatoma cells. The results strongly suggest that HPO acts as an autocrine factor for hepatoma cells in vitro.

Aged↗
PubMed2001

Genetic analysis of Brugada syndrome in Israel: two novel mutations and possible genetic heterogeneity.

Idiopathic ventricular fibrillation in patients with an electrocardiogram (ECG) pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (now frequently called Brugada syndrome) is associated with a high incidence of syncopal episodes or sudden death. The disease is inherited as an autosomal dominant trait. Mutations in SCN5A, a cardiac sodium channel gene, have been recently associated with Brugada syndrome. We have analyzed 7 patients from Israel affected with Brugada syndrome. The families of these patients are characterized by a small number of symptomatic members. Sequencing analysis of SCN5A revealed two novel mutations, G35S and R104Q, in two Brugada patients, and a possible R34C polymorphism in two unrelated controls. No mutations were detected in 5 other patients, suggesting genetic heterogeneity. Low penetrance is probably the cause for the small number of symptomatic members in the two families positive for the SCN5A mutations.

Adult↗
PubMed2001

Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: a nested case-control study in Taiwan.

This study was conducted to investigate the modifying effect of glutathione S-transferase (GST) M1 and T1 polymorphisms on aflatoxin-induced hepatocarcinogenesis among chronic hepatitis B virus surface antigen (HBsAg) carriers. A total of 79 HBsAg-positive cases of hepatocellular carcinoma (HCC) diagnosed between 1991 and 1997 were identified and individually matched to one or two HBsAg-positive controls on age, gender, residence and date of recruitment from the same cancer screening cohort in Taiwan. Blood samples were tested for hepatitis B and C viral markers by enzyme immunoassay and for aflatoxin B(1) (AFB(1))-albumin adducts by competitive enzyme-linked immunosorbent assay. GSTM1 and GSTT1 genotypes were determined by PCR. There was a statistically significant relationship between detectable levels of AFB(1)-albumin adducts in serum and risk of HCC among chronic HBsAg carriers, with an adjusted odds ratio (OR) of 2.0 [95% confidence interval (CI) 1.1-3.7]. In addition, the effect of aflatoxin exposure on HCC risk was more pronounced among chronic HBsAg carriers with the GSTT1 null genotype (OR 3.7, 95% CI 1.5-9.3) than those who were non-null (OR 0.9, 95% CI 0.3-2.4). The interaction between serum AFB(1)-albumin adduct level and GSTT1 genotype was statistically significant (P = 0.03). For GSTM1 the effect of aflatoxin exposure on HCC risk in those with the null genotype was also greater (adjusted OR 2.8, 95% CI 1.0-7.8) than in those with the gene present (adjusted OR 1.8, 95% CI 0.8-4.5), but the difference was not significant (P = 0.91). Notably, when the interaction between aflatoxin exposure and GSTT1 genotype was considered, aflatoxin exposure by itself was not a significant determinant of HCC risk among chronic HBsAg carriers. These results demonstrate the importance of gene-environment interactions in the multifactorial development of HCC.

Adult↗
PubMed2001

Role of protein synthesis in the development of a transcriptionally permissive state in one-cell stage mouse embryos.

The time of onset of gene transcription in the mouse embryo is temporally regulated. A prominent feature of this regulation is a change during the one-cell stage from a transcriptionally nonpermissive state to a transcriptionally permissive state. During the early one-cell stage, the cytoplasm is either inadequate or suppressive for nuclear gene transcription, but by the late one-cell stage, the cytoplasm acquires the ability to support gene transcription either in endogenous nuclei or exogenous nuclei introduced microsurgically. We have investigated the role of protein synthesis in this cytoplasmic transition. Nuclei from two-cell stage embryos treated with alpha-amanitin were used to evaluate the transcriptional permissiveness of late one-cell stage cytoplasm, as indicated by the production of transcripts from four genes that are specifically transcribed at elevated rates during the two-cell stage. Two of these genes were transcribed following nuclear transfer to late one-cell stage cytoplasm, and two were not transcribed. Treatment of the recipient cytoplasm with cycloheximide to inhibit protein synthesis from the early to the late one-cell stage inhibited the transcription of the two genes that were transcribed in the untreated, late one-cell stage recipients. These results indicate that acquisition of the transcriptionally permissive state during the one-cell stage is facilitated by protein synthesis, and that the transcriptional permissiveness in the late one-cell stage cytoplasm is limited to certain genes.

Amanitins↗
PubMed2001

Analysis of the cat eye syndrome critical region in humans and the region of conserved synteny in mice: a search for candidate genes at or near the human chromosome 22 pericentromere.

We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R, ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny are CECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 and CECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located approximately 1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.

Abnormalities, Multiple↗
PubMed2001

Amino acid residues critical for differential inhibition of CYP2B4, CYP2B5, and CYP2B1 by phenylimidazoles.

The molecular basis for reversible inhibition of rabbit CYP2B4 and CYP2B5 and rat CYP2B1 by phenylimidazoles was assessed with active-site mutants and new three-dimensional models based on the crystal structure of CYP2C5. 4-Phenylimidazole was 17- to 32-fold more potent toward CYP2B4 and CYP2B1 than CYP2B5. The 3D models, along with site-directed mutagenesis data, revealed the importance of residue 114 for sensitivity to inhibition of all three CYP2B enzymes. Besides Ile 114, Val 367 was also found to be critical for inhibition of CYP2B4 and CYP2B1. The most interesting new insights were obtained from analysis of the CYP2B5 model and the CYP2B5 active-site mutants. Simultaneous substitution of residues 114, 294, 363, and 367 with the corresponding residues of CYP2B4 decreased the IC(50) value for inhibition by 4-phenylimidazole 12-fold. Docking 4-phenylimidazole into the models of CYP2B5 mutants demonstrated that the inhibitor-binding site is strongly influenced by residue-residue interactions, especially between residues 114 and 294. A chlorine substitution at position 4 of the phenyl moiety of 4- and 1-phenylimidazole resulted in IC(50) values 95- and 130-fold lower for CYP2B4 than for CYP2B5, respectively, suggesting that these compounds are selective inhibitors of CYP2B4. Overall, the study revealed that differences in the determinants of inhibition between CYP2B4 and CYP2B5 are caused not only by single residue inhibitor contacts but also by residue-residue interactions. This new generation of CYP2B models may provide valuable information for the design of selective inhibitors of human CYP2B6 and for the development of drugs that avoid drug interactions due to P450 inhibition.

Amino Acid Sequence↗
PubMed2001

WdChs2p, a class I chitin synthase, together with WdChs3p (class III) contributes to virulence in Wangiella (Exophiala) dermatitidis.

The chitin synthase structural gene WdCHS2 was isolated by screening a subgenomic DNA library of Wangiella dermatitidis by using a 0.6-kb PCR product of the gene as a probe. The nucleotide sequence revealed a 2,784-bp open reading frame, which encoded 928 amino acids, with a 59-bp intron near its 5' end. Derived protein sequences showed highest amino acid identities with those derived from the CiCHS1 gene of Coccidioides immitis and the AnCHSC gene of Aspergillus nidulans. The derived sequence also indicated that WdChs2p is an orthologous enzyme of Chs1p of Saccharomyces cerevisiae, which defines the class I chitin synthases. Disruptions of WdCHS2 produced strains that showed no obvious morphological defects in yeast vegetative growth or in ability to carry out polymorphic transitions from yeast cells to hyphae or to isotropic forms. However, assays showed that membranes of wdchs2Delta mutants were drastically reduced in chitin synthase activity. Other assays of membranes from a wdchs1Deltawdchs3Deltawdchs4Delta triple mutant showed that their residual chitin synthase activity was extremely sensitive to trypsin activation and was responsible for the majority of zymogenic activity. Although no loss of virulence was detected when wdchs2Delta strains were tested in a mouse model of acute infection, wdchs2Deltawdchs3Delta disruptants were considerably less virulent in the same model, even though wdchs3Delta strains also had previously shown no loss of virulence. This virulence attenuation in the wdchs2Deltawdchs3Delta mutants was similarly documented in a limited fashion in more-sensitive cyclophosphamide-induced immunocompromised mice. The importance of WdChs2p and WdChs3p to the virulence of W. dermatitidis was then confirmed by reconstituting virulence in the double mutant by the reintroduction of either WdCHS2 or WdCHS3 into the wdchs2Deltawdchs3Delta mutant background.

Amino Acid Sequence↗
PubMed2001

Micrococci and peptidoglycan activate TLR2-->MyD88-->IRAK-->TRAF-->NIK-->IKK-->NF-kappaB signal transduction pathway that induces transcription of interleukin-8.

This study was done to elucidate the signal transduction pathway of interleukin-8 (IL-8) induction by gram-positive bacteria. Bacteria (micrococci) and peptidoglycan (PGN) induced transcription of IL-8 in HEK293 cells expressing Toll-like receptor 2 (TLR2) and CD14 but not in those expressing TLR1 or TLR4. A mutation within the NF-kappaB site in the IL-8 promoter abrogated transcriptional induction of IL-8 by the two stimulants. Dominant negative myeloid differentiation protein (MyD88), IL-1 receptor-associated kinase (IRAK), NFkappaB-inducing kinase (NIK), and IkappaB kinase (IKK) mutant forms completely inhibited micrococcus- and PGN-induced activation of NF-kappaB and expression of the gene for IL-8. Induction of NF-kappaB was partially inhibited by dominant negative tumor necrosis factor receptor-associated kinase 6 (TRAF6) but not TRAF2, whereas induction of IL-8 gene was partially inhibited by both TRAF6 and TRAF2. These data indicate that micrococci and PGN induce TLR2-dependent activation of the gene for IL-8 and that this activation requires MyD88, IRAK, NIK, IKK, and NF-kappaB and may also utilize TRAF6 and, to a lesser extent, TRAF2.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Increase in plasma adrenomedullin in patients with heart failure characterised by diastolic dysfunction.

OBJECTIVE: To investigate the relation between plasma adrenomedullin and the severity of diastolic dysfunction in patients with heart failure. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENTS: 77 patients (mean (SEM) age 66.3 (1.2) years; 75% male) who were being followed in the outpatient clinic after admission to hospital for acute heart failure. INTERVENTIONS: Same day echocardiography with Doppler studies; determination of venous adrenomedullin concentration by radioimmunoassay. MAIN OUTCOME MEASURES: Plasma adrenomedullin concentration and its correlation with systolic and diastolic function. RESULTS: 31 patients (40%) had isolated diastolic dysfunction (ejection fraction > 50%), and the remaining 46 had a depressed ejection fraction (< 50%). Of the patients with diastolic dysfunction, 17 had a restrictive filling pattern. In all but one of these there was coexisting systolic failure (chi(2) = 10.7, p = 0.001). Patients with systolic heart failure and a restrictive filling pattern (group 1, n = 16) had a higher plasma adrenomedullin than those with systolic failure and a non-restrictive filling pattern (group 2, n = 30) or with isolated diastolic heart failure and a non-restrictive filling pattern (group 3, n = 30) (mean (SEM): 91.7 (21.1) v 38.4 (8.8) v 34.0 (6.5) pmol/l, both p < 0.05). All heart failure values were higher (p < 0.01) than the control value (6.9 (1.2) pmol/l). Ejection fraction and left ventricular dimensions were similar in groups 1 and 2. Plasma adrenomedullin did not correlate with ejection fraction or New York Heart Association functional class. Stepwise multiple regression analysis showed that the presence of a restrictive filling pattern was the only independent variable associated with a high plasma adrenomedullin. CONCLUSIONS: Plasma adrenomedullin concentrations in patients with heart failure are determined by the presence of diastolic dysfunction, and are especially raised in the presence of a restrictive filling pattern. There appears to be no correlation with systolic dysfunction.

Acute Disease↗
PubMed2001

Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation.

Idiopathic ventricular fibrillation (IVF) can cause sudden death in both adults and children. One form of IVF (Brugada syndrome), characterized by S-T segment elevation (STE) in the electrocardiogram, has been linked to mutations of SCN5A, the gene encoding the voltage-gated cardiac Na(+) channel. A missense mutation of SCN5A that substitutes glutamine for leucine at codon 567 (L567Q, in the cytoplasmic linker between domains I and II) is identified with sudden infant death and Brugada syndrome in one family. However, neither the functional effect of the L567Q mutation nor the molecular mechanism underlying the pathogenicity of the mutation is known. Patch-clamp analysis of L567Q channels expressed in human embryonic kidney cells revealed a marked acceleration and a negative shift in the voltage dependence of inactivation. Unlike other Brugada mutations, this phenotype was expressed independently of temperature or auxiliary beta(1)-subunits. These results support a proposed linkage between Brugada syndrome and some instances of sudden infant death and the hypothesis that reduced Na(+) conductance is the primary cause of IVF with STE.

Cell Line↗
PubMed2001

Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice.

Sepsis is associated with increased intestinal permeability, but mediators and mechanisms are not fully understood. We examined the role of interleukin (IL)-6 and IL-10 in sepsis-induced increase in intestinal permeability. Intestinal permeability was measured in IL-6 knockout (IL-6 -/-) and wild-type (IL-6 +/+) mice 16 h after induction of sepsis by cecal ligation and puncture or sham operation. In other experiments, mice or intestinal segments incubated in Ussing chambers were treated with IL-6 or IL-10. Intestinal permeability was assessed by determining the transmucosal transport of the 4.4-kDa marker fluorescein isothiocyanate conjugated dextran and the 40-kDa horseradish peroxidase. Intestinal permeability for both markers was increased in septic IL-6 +/+ mice but not in septic IL-6 -/- mice. Treatment of nonseptic mice or of intestinal segments in Ussing chambers with IL-6 did not influence intestinal permeability. Plasma IL-10 levels were increased in septic IL-6 -/- mice, and treatment of septic mice with IL-10 resulted in reduced intestinal permeability. Increased intestinal permeability during sepsis may be regulated by an interaction between IL-6 and IL-10. Treatment with IL-10 may prevent the increase in mucosal permeability during sepsis.

Animals↗
PubMed2001

Prevalence of emphysema in individuals who underwent screening CT for lung cancer in Nagano prefecture of Japan.

BACKGROUND: Screening for lung cancer with low-dose spiral computed tomography (CT) was carried out in Nagano prefecture in Japan. OBJECTIVE: To study the prevalence of emphysema in 7,847 individuals based on the Nagano spiral CT screening and to correlate the prevalence and severity of emphysema with various factors. METHODS: Spiral CT images with scan parameters of 120 kV, 50 mA, 10-mm collimation and a pitch of 2 obtained at full inspiration were retrospectively evaluated in 7,847 individuals. Emphysema was defined as the presence of low-attenuation areas in the lung parenchyma. Extent of emphysema was graded on a four-level scale and correlated with gender, age and smoking habits. RESULTS: There were 4,288 males and 3,559 females. Mean age of the subjects was 61 years; 45.8% of the participants were smokers. Overall prevalence of emphysema was 2.9%; the prevalence was significantly higher in males (5.0%) than in females (0.5%); it was also significantly higher in smokers, and increased with age. Emphysema was positively correlated with age, but there was no correlation with smoking indices. Emphysema was mostly mild and localized in the upper lung. The logistic model revealed that gender, age and smoking indices were significant factors for developing emphysema. CONCLUSIONS: Overall prevalence of emphysema was 2.9%. The prevalence was higher in males and in older people. Smoking was also related to a higher prevalence of emphysema but not to its severity.

Adult↗
PubMed2001

Identification and molecular characterization of de novo translocation t(8;14)(q22.3;q13) associated with a vascular and tissue overgrowth syndrome.

Klippel-Trenaunay syndrome (KTS) is a disorder primarily characterized by capillary-venous vascular malformations associated with altered limb bulk and/or length. We report the identification of a balanced translocation involving chromosomes 8q22.3 and 14q13 in a patient with a vascular and tissue overgrowth syndrome consistent with KTS. We demonstrated that translocation t(8;14)(q22.3;q13) arose de novo. These data suggest that a pathogenic gene for a vascular and tissue overgrowth syndrome (KTS) may be located at chromosome 8q22.3 or 14q13. Fluorescence in situ hybridization (FISH) analysis was used to define the breakpoint on chromosome 8q22.3 to a <5-cM interval flanked by markers AFMA082TG9 and GATA25E10, and the 14q13 breakpoint within a 1-cM region between STSs WI-6583 and D14S989. This study provides a framework for the fine-mapping and ultimate cloning of a novel vascular gene at 8q22.3 or 14q13.

Adolescent↗
PubMed2001

Spatial expression patterns of peptide transporters in the human and rat gastrointestinal tracts, Caco-2 in vitro cell culture model, and multiple human tissues.

This study sought to identify the spatial patterns of expression of peptide transporter 1 (PepT1), peptide transporter 3 (PTR3), peptide/histidine transporter 1 (PHT1), and the human peptide transporter 1 (HPT-1) mRNA in complementary DNA (cDNA) libraries of the human and rat gastrointestinal tracts (GIT), Caco-2 in vitro cell culture model, and in a human multiple tissue panel. Human PTR3 and PHT1 are putative peptide transporters recently discovered. Using sequence-specific primers designed to amplify regions of PepT1, PTR3, PHT1, and HPT-1, we were able to identify the expression of mRNA for each of these transporters in human cDNA panels (Clontech, Palo Alto, CA), the rat GIT, and in Caco-2 cDNA libraries by the polymerase chain reaction (PCR) and Southern Blot analysis. These studies suggest that in the human GIT, PepT1 appears to be localized predominantly in the duodenum, with decreasing expression in the jejunum and ileum. In contrast, PTR3 and HPT-1 were widely expressed in the human GIT, with predominant expression in the different regions of the colon. PHT1 appeared to be expressed in low levels throughout the human GI tract. Interestingly, the mRNAs for all 4 peptide transporters were expressed in Caco-2 cells throughout 30 days of culture. PepT1, PTR3, PHT1, and HPT-1 were also widely expressed in the rat GIT. Human tissue cDNA panel screening suggests that PTR3 and PHT1 are more uniformly expressed, whereas PepT1 and HPT-1 demonstrated site-specific expression. These results suggest that PepT1, PTR3, PHT1, and HPT-1 all may act to facilitate the diffusion of peptides and peptide-based pharmaceuticals in the GIT. PTR3, PHT1, and HPT-1 expressions in Caco-2 cell monolayers strongly suggest that their function needs to be further elucidated and their contribution to peptide transport not ignored. Taken together, these results demonstrate the potential for molecular biological characterization in localizing active transporter systems that can potentially be targeted for enhancing the absorption of peptide-based pharmaceuticals.

Animals↗
PubMed2001

Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains.

Fibroblast growth factor receptors (FGFR) 1 and 3 have distinct mitogenic activities in vitro. In several cultured cell lines, FGFR1 transmits a potent mitogenic signal, whereas FGFR3 has little or no mitogenic activity. However, in other in vitro assays the FGFR3 intracellular domain is comparable with that of FGFR1. In vivo, FGFR3 negatively regulates chondrocyte proliferation and differentiation, and activating mutations are the molecular etiology of achondroplasia. By contrast, FGFR1 transmits a proliferative signal in various cell types in vivo. These observations suggest that inhibition of the proliferating chondrocyte could be a unique property of FGFR3 or, alternatively, a unique property of the proliferating chondrocyte. To test this hypothesis, FGFR1 signaling was activated in the growth plate in cells that normally express FGFR3. Comparison of transgenic mice with an activated FGFR1 signaling pathway with an achondroplasia-like mouse that expresses a similarly activated FGFR3 signaling pathway demonstrated that both transgenes result in a similar achondroplasia-like dwarfism. These data demonstrate that suppression of mitogenic activity by FGFR signaling is a property that is unique to growth plate chondrocytes. Surprisingly, we observed that in transgenic mice expressing an activated FGFR, some synovial joints failed to develop and were replaced by cartilage. The defects in the digit joints phenocopied the symphalangism that occurs in Apert syndrome and the number of affected joints was dependent on transgene dose. In contrast to the phenotype in the growth plate, the joint phenotype was more severe in transgenic mice with an activated FGFR1 signaling pathway. The failure of joint development resulted from expanded chondrification in the presumptive joint space, suggesting a crucial role for FGF signaling in regulating the transition of condensed mesenchyme to cartilage and in defining the boundary of skeletal elements.

Animals↗