Research ExplorerPublicationsGene disruption of Spred-2 causes dwarfism

Gene disruption of Spred-2 causes dwarfism

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Gene disruption of Spred-2 causes dwarfism. / Bundschu, Karin; Knobeloch, Klaus-Peter; Ullrich, Melanie; Schinke, Thorsten; Amling, Michael; Engelhardt, Catherine M; Renné, Thomas; Walter, Ulrich; Schuh, Kai.

In: J BIOL CHEM, Vol. 280, No. 31, 05.08.2005, p. 28572-80.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bundschu, K, Knobeloch, K-P, Ullrich, M, Schinke, T, Amling, M, Engelhardt, CM, Renné, T, Walter, U & Schuh, K 2005, 'Gene disruption of Spred-2 causes dwarfism', J BIOL CHEM, vol. 280, no. 31, pp. 28572-80. https://doi.org/10.1074/jbc.M503640200

APA

Bundschu, K., Knobeloch, K-P., Ullrich, M., Schinke, T., Amling, M., Engelhardt, C. M., Renné, T., Walter, U., & Schuh, K. (2005). Gene disruption of Spred-2 causes dwarfism. J BIOL CHEM, 280(31), 28572-80. https://doi.org/10.1074/jbc.M503640200

Vancouver

Bundschu K, Knobeloch K-P, Ullrich M, Schinke T, Amling M, Engelhardt CM et al. Gene disruption of Spred-2 causes dwarfism. J BIOL CHEM. 2005 Aug 5;280(31):28572-80. https://doi.org/10.1074/jbc.M503640200

Bibtex

@article{39c8c6c91609478fbdf91eb573cd98ba,
title = "Gene disruption of Spred-2 causes dwarfism",
abstract = "The impact of the fibroblast growth factor receptor 3 (FGFR3)-mediated signaling pathway on bone growth has been demonstrated by various genetic approaches. Overexpression of fibroblast growth factors (FGFs), several gain-of-function mutations in the FGFR3, and constitutive activation of mitogen-activated protein kinase (MAPK) kinase (MEK1) in chondrocytes have been shown to cause dwarfism in mice by activation of the MAPK signaling pathway. To investigate the previously reported inhibitory role of Spred in the FGFR3/MAPK pathway, we generated mice with a trapped Spred-2 gene. Here we show that lack of functional Spred-2 protein in mice caused a dwarf phenotype, similar to achondroplasia, the most common form of human dwarfism. Spred-2(-/-) mice showed reduced growth and body weight, they had a shorter tibia length, and showed narrower growth plates as compared with wild-type mice. We detected promoter activity and protein expression of Spred-2 in chondrocytes, suggesting an important function of Spred-2 in chondrocytes and bone development. Stimulation of chondrocytes with different FGF concentrations showed earlier and augmented ERK phosphorylation in Spred-2(-/-) chondrocytes in comparison to Spred-2(+/+) chondrocytes. Our observations suggest a model in which loss of Spred-2 inhibits bone growth by inhibiting chondrocyte differentiation through up-regulation of the MAPK signaling pathway.",
keywords = "Animals, Bone Development, Dwarfism, Female, Gene Deletion, Genetic Vectors, Humans, Male, Mice, Mice, Knockout, Mice, Transgenic, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction",
author = "Karin Bundschu and Klaus-Peter Knobeloch and Melanie Ullrich and Thorsten Schinke and Michael Amling and Engelhardt, {Catherine M} and Thomas Renn{\'e} and Ulrich Walter and Kai Schuh",
year = "2005",
month = aug,
day = "5",
doi = "10.1074/jbc.M503640200",
language = "English",
volume = "280",
pages = "28572--80",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "31",

}

RIS

TY - JOUR

T1 - Gene disruption of Spred-2 causes dwarfism

AU - Bundschu, Karin

AU - Knobeloch, Klaus-Peter

AU - Ullrich, Melanie

AU - Schinke, Thorsten

AU - Amling, Michael

AU - Engelhardt, Catherine M

AU - Renné, Thomas

AU - Walter, Ulrich

AU - Schuh, Kai

PY - 2005/8/5

Y1 - 2005/8/5

N2 - The impact of the fibroblast growth factor receptor 3 (FGFR3)-mediated signaling pathway on bone growth has been demonstrated by various genetic approaches. Overexpression of fibroblast growth factors (FGFs), several gain-of-function mutations in the FGFR3, and constitutive activation of mitogen-activated protein kinase (MAPK) kinase (MEK1) in chondrocytes have been shown to cause dwarfism in mice by activation of the MAPK signaling pathway. To investigate the previously reported inhibitory role of Spred in the FGFR3/MAPK pathway, we generated mice with a trapped Spred-2 gene. Here we show that lack of functional Spred-2 protein in mice caused a dwarf phenotype, similar to achondroplasia, the most common form of human dwarfism. Spred-2(-/-) mice showed reduced growth and body weight, they had a shorter tibia length, and showed narrower growth plates as compared with wild-type mice. We detected promoter activity and protein expression of Spred-2 in chondrocytes, suggesting an important function of Spred-2 in chondrocytes and bone development. Stimulation of chondrocytes with different FGF concentrations showed earlier and augmented ERK phosphorylation in Spred-2(-/-) chondrocytes in comparison to Spred-2(+/+) chondrocytes. Our observations suggest a model in which loss of Spred-2 inhibits bone growth by inhibiting chondrocyte differentiation through up-regulation of the MAPK signaling pathway.

AB - The impact of the fibroblast growth factor receptor 3 (FGFR3)-mediated signaling pathway on bone growth has been demonstrated by various genetic approaches. Overexpression of fibroblast growth factors (FGFs), several gain-of-function mutations in the FGFR3, and constitutive activation of mitogen-activated protein kinase (MAPK) kinase (MEK1) in chondrocytes have been shown to cause dwarfism in mice by activation of the MAPK signaling pathway. To investigate the previously reported inhibitory role of Spred in the FGFR3/MAPK pathway, we generated mice with a trapped Spred-2 gene. Here we show that lack of functional Spred-2 protein in mice caused a dwarf phenotype, similar to achondroplasia, the most common form of human dwarfism. Spred-2(-/-) mice showed reduced growth and body weight, they had a shorter tibia length, and showed narrower growth plates as compared with wild-type mice. We detected promoter activity and protein expression of Spred-2 in chondrocytes, suggesting an important function of Spred-2 in chondrocytes and bone development. Stimulation of chondrocytes with different FGF concentrations showed earlier and augmented ERK phosphorylation in Spred-2(-/-) chondrocytes in comparison to Spred-2(+/+) chondrocytes. Our observations suggest a model in which loss of Spred-2 inhibits bone growth by inhibiting chondrocyte differentiation through up-regulation of the MAPK signaling pathway.

KW - Animals

KW - Bone Development

KW - Dwarfism

KW - Female

KW - Gene Deletion

KW - Genetic Vectors

KW - Humans

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Repressor Proteins

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1074/jbc.M503640200

DO - 10.1074/jbc.M503640200

M3 - SCORING: Journal article

C2 - 15946934

VL - 280

SP - 28572

EP - 28580

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 31

ER -