0.1 microM endothelin 3 (ET3), 1 microM angiotensin II (AII), and 10 microM acetylcholine (Ach) significantly increased AVP release; ET3 (C 1.78 +/- 0.20 vs. ET3 6.85 +/- 1.86 pg/2 x 10(6) cells, N = 8, P < 0.02); AII (C 1.29 +/- 0.38 vs. AII 27.80 +/- 7.09 pg/2 x 10(6) cells, N = 5, P < 0.05) and Ach (C 1.14 +/- 0.33 vs. Ach 2.68 +/- 0.58 pg/2 x x10(6) cells, N = 6, P < 0.05).
0.1 microM endothelin 3 (ET3), 1 microM angiotensin II (AII), and 10 microM acetylcholine (Ach) significantly increased AVP release; ET3 (C 1.78 +/- 0.20 vs. ET3 6.85 +/- 1.86 pg/2 x 10(6) cells, N = 8, P < 0.02); AII (C 1.29 +/- 0.38 vs. AII 27.80 +/- 7.09 pg/2 x 10(6) cells, N = 5, P < 0.05) and Ach (C 1.14 +/- 0.33 vs. Ach 2.68 +/- 0.58 pg/2 x x10(6) cells, N = 6, P < 0.05).
We now report the linkage for the Ellis-van Creveld syndrome gene to markers on the distal short arm of human chromosome 4, with Zmax = 6.91 at theta = 0.02 for marker HOX7, in a region proximal to the FGFR3 gene responsible for the achondroplasia phenotype.
0.1 microM endothelin 3 (ET3), 1 microM angiotensin II (AII), and 10 microM acetylcholine (Ach) significantly increased AVP release; ET3 (C 1.78 +/- 0.20 vs. ET3 6.85 +/- 1.86 pg/2 x 10(6) cells, N = 8, P < 0.02); AII (C 1.29 +/- 0.38 vs. AII 27.80 +/- 7.09 pg/2 x 10(6) cells, N = 5, P < 0.05) and Ach (C 1.14 +/- 0.33 vs. Ach 2.68 +/- 0.58 pg/2 x x10(6) cells, N = 6, P < 0.05).
We now report the linkage for the Ellis-van Creveld syndrome gene to markers on the distal short arm of human chromosome 4, with Zmax = 6.91 at theta = 0.02 for marker HOX7, in a region proximal to the FGFR3 gene responsible for the achondroplasia phenotype.
The sequence changes were used to demonstrate discordant segregation between the COL10A1 locus and achondroplasia and pseudoachondroplasia, in nuclear families.
These results indicate that mutations at the chondroitin sulfate proteoglycan core protein locus do not cause achondroplasia or pseudoachondroplasia in these families.
Two lines of evidence speak against mutation in COL2A1 as the cause of achondroplasia: (1) no gross rearrangements are seen on Southern blot analysis of DNA from probands, and (2) linkage studies in multiplex families demonstrate discordant inheritance of achondroplasia and COL2A1 alleles.
Here we use quantitative Fӧster Resonance Energy Transfer (FRET) and osmotically derived plasma membrane vesicles to study the effect of the achondroplasia mutation on the early stages of FGFR3 signaling in response to the ligands fgf1 and fgf2.
A regulation that occurs mainly in the mesomelic segments, a region where SHOX is known to be strongly expressed, offers a possible explanation for the phenotypes seen in patients with FGFR3 (e.g. achondroplasia) and SHOX defects (e.g.Léri-Weill dyschondrosteosis).
Our study also found that the premature fusion of cranial synchondroses in ACH mice was partially corrected after the PTH (1-34) treatment, suggesting that the PTH treatment may rescue the progressive narrowing of neurocentral synchondroses that cannot be readily corrected by surgery.
The phenotypes of combined LWD and achondroplasia or hypochondroplasia appeared to be less than additive, suggesting that SHOX and FGFR3 act on overlapping pathways of bone growth and development.
Using our established techniques for single-cell ratiometric real-time calcium image analysis, we defined the nature of the basic fibroblast growth factor (bFGF)-induced calcium signal in human diploid fibroblasts, and, in blinded studies, have analyzed the bFGF-induced signals from 18 independent fibroblast cell lines, including multiple lines from patients with known mutant alleles of FGFR3 and syndromes of Ach or TD.
Gain-of-function variants in several FGF receptors (FGFRs) are implicated in a wide spectrum of growth disorders from achondroplasia to overgrowth syndromes.
Here we use quantitative Fӧster Resonance Energy Transfer (FRET) and osmotically derived plasma membrane vesicles to study the effect of the achondroplasia mutation on the early stages of FGFR3 signaling in response to the ligands fgf1 and fgf2.
The increased expression of PTHrP and down-regulated FGFR3 level may be responsible for the positive effects of PTH on bone phenotype of ACH and TDII mice.
TDI-FGFR3 was not highly phosphorylated under ligand-free conditions, but the peak phosphorylation levels of TDI-FGFR3 and ACH-FGFR3 were maintained for 30 min after stimulation with FGF-1.
Preliminary data indicate that recombinant C-type natriuretic peptide (CNP) is safe in children and increases growth velocity upon 42 months of treatment in achondroplasia.