Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice.
Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice.
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DOI：
10.1242/dmm.012849
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发表时间：
2013-11
影响因子：
4.3
通讯作者：
King PD
中科院分区：
文献类型：
--
作者：
Lapinski PE;Meyer MF;Feng GS;Kamiya N;King PD
In mice, induced global disruption of the Ptpn11 gene, which encodes the SHP-2 tyrosine phosphatase, results in severe skeletal abnormalities. To understand the extent to which skeletal abnormalities can be attributed to perturbation of SHP-2 function in bone-forming osteoblasts and chondrocytes, we generated mice in which disruption of Ptpn11 is restricted to mesenchymal stem cells (MSCs) and their progeny, which include both cell types. MSC-lineage-specific SHP-2 knockout (MSC SHP-2 KO) mice exhibited postnatal growth retardation, limb and chest deformity, and calvarial defects. These skeletal abnormalities were associated with an absence of mature osteoblasts and massive chondrodysplasia with a vast increase in the number of terminally differentiated hypertrophic chondrocytes in affected bones. Activation of mitogen activated protein kinases (MAPKs) and protein kinase B (PKB; also known as AKT) was impaired in bone-forming cells of MSC SHP-2 KO mice, which provides an explanation for the skeletal defects that developed. These findings reveal a cell-autonomous role for SHP-2 in bone-forming cells in mice in the regulation of skeletal development. The results add to our understanding of the pathophysiology of skeletal abnormalities observed in humans with germline mutations in the PTPN11 gene (e.g. Noonan syndrome and LEOPARD syndrome).
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影响因子：
19.7
作者：
KENNEDY, LA
通讯作者：
KENNEDY, LA
影响因子：
3.5
作者：
Hanna, Nadine;Montagner, Alexandra;Raynal, Patrick
通讯作者：
Raynal, Patrick
影响因子：
4.3
作者：
Bauler TJ;Kamiya N;Lapinski PE;Langewisch E;Mishina Y;Wilkinson JE;Feng GS;King PD
通讯作者：
King PD
影响因子：
4.8
作者：
Keilhack, H;David, FS;Neel, BG
通讯作者：
Neel, BG
影响因子：
5.7
作者：
Barford, D;Neel, BG
通讯作者：
Neel, BG