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@article{1797299,
author = {Hrubá, Eva and Kavková, Michaela and Dalecká, Linda and Macholán, Miloš and Zikmund, Tomáš and Vařecha, Miroslav and Bosáková, Michaela and Kaiser, Jozef and Krejčí, Pavel and Hovořáková, Mária and Buchtová, Marcela},
article_number = {11},
doi = {http://dx.doi.org/10.1002/jbmr.4427},
keywords = {BONE QCT/mu CT; ANALYSIS/QUANTITATION OF BONE; GENETIC ANIMAL MODELS; MOLECULAR PATHWAYS - DEVELOPMENT; LIMB PATTERNING; BONE MODELING AND REMODELING; HEDGEHOG; CELL/TISSUE SIGNALING},
language = {eng},
issn = {0884-0431},
journal = {Journal of Bone and Mineral Research},
title = {Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling},
url = {https://doi.org/10.1002/jbmr.4427},
volume = {36},
year = {2021}
}
TY - JOUR
ID - 1797299
AU - Hrubá, Eva - Kavková, Michaela - Dalecká, Linda - Macholán, Miloš - Zikmund, Tomáš - Vařecha, Miroslav - Bosáková, Michaela - Kaiser, Jozef - Krejčí, Pavel - Hovořáková, Mária - Buchtová, Marcela
PY - 2021
TI - Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling
JF - Journal of Bone and Mineral Research
VL - 36
IS - 11
SP - 2258-2274
EP - 2258-2274
PB - American Society for Bone and Mineral Research
SN - 08840431
KW - BONE QCT/mu CT
KW - ANALYSIS/QUANTITATION OF BONE
KW - GENETIC ANIMAL MODELS
KW - MOLECULAR PATHWAYS - DEVELOPMENT
KW - LIMB PATTERNING
KW - BONE MODELING AND REMODELING
KW - HEDGEHOG
KW - CELL/TISSUE SIGNALING
UR - https://doi.org/10.1002/jbmr.4427
N2 - The Sprouty family is a highly conserved group of intracellular modulators of receptor tyrosine kinase (RTK)-signaling pathways, which have been recently linked to primary cilia. Disruptions in the structure and function of primary cilia cause inherited disorders called ciliopathies. We aimed to evaluate Sprouty2 and Sprouty4 gene-dependent alterations of ciliary structure and to focus on the determination of its association with Hedgehog signaling defects in chondrocytes. Analysis of the transgenic mice phenotype with Sprouty2 and Sprouty4 deficiency revealed several defects, including improper endochondral bone formation and digit patterning, or craniofacial and dental abnormalities. Moreover, reduced bone thickness and trabecular bone mass, skull deformities, or chondromalike lesions were revealed. All these pathologies might be attributed to ciliopathies. Elongation of the ciliary axonemes in embryonic and postnatal growth plate chondrocytes was observed in Sprouty2(-/-) and Sprouty2(+/-)/Sprouty4(-/-) mutants compared with corre- sponding littermate controls. Also, cilia-dependent Hedgehog signaling was upregulated in Sprouty2/4 mutant animals. Ptch1 and Ihh expression were upregulated in the autopodium and the proximal tibia of Sprouty2(-/-)/Sprouty4(-/-) mutants. Increased levels of the GLI3 repressor (GLI3R) form were detected in Sprouty2/4 mutant primary fibroblast embryonic cell cultures and tissues. These findings demonstrate that mouse lines deficient in Sprouty proteins manifest phenotypic features resembling ciliopathic phenotypes in multiple aspects and may serve as valuable models to study the association between overactivation of RTK and dysfunction of primary cilia during skeletogenesis.
ER -
HRUBÁ, Eva, Michaela KAVKOVÁ, Linda DALECKÁ, Miloš MACHOLÁN, Tomáš ZIKMUND, Miroslav VAŘECHA, Michaela BOSÁKOVÁ, Jozef KAISER, Pavel KREJČÍ, Mária HOVOŘÁKOVÁ and Marcela BUCHTOVÁ. Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling. \textit{Journal of Bone and Mineral Research}. American Society for Bone and Mineral Research, vol.~36, No~11, p.~2258-2274. ISSN~0884-0431. doi:10.1002/jbmr.4427. 2021.
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