PMID- 24077964
OWN - NLM
STAT- MEDLINE
DCOM- 20140617
LR  - 20211021
IS  - 1754-8411 (Electronic)
IS  - 1754-8403 (Print)
IS  - 1754-8403 (Linking)
VI  - 6
IP  - 6
DP  - 2013 Nov
TI  - Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and 
      chest deformity, and calvarial defects in mice.
PG  - 1448-58
LID - 10.1242/dmm.012849 [doi]
AB  - 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).
FAU - Lapinski, Philip E
AU  - Lapinski PE
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI 48109, USA.
FAU - Meyer, Melissa F
AU  - Meyer MF
FAU - Feng, Gen-Sheng
AU  - Feng GS
FAU - Kamiya, Nobuhiro
AU  - Kamiya N
FAU - King, Philip D
AU  - King PD
LA  - eng
GR  - R01 HL096498/HL/NHLBI NIH HHS/United States
GR  - HL096498/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130925
PL  - England
TA  - Dis Model Mech
JT  - Disease models & mechanisms
JID - 101483332
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
SB  - IM
MH  - Animals
MH  - Bone and Bones/*abnormalities
MH  - Fetal Growth Retardation/*genetics
MH  - Limb Deformities, Congenital/*genetics
MH  - Mesenchymal Stem Cells/*enzymology
MH  - Mice
MH  - Mice, Knockout
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/*metabolism
MH  - Thorax/*abnormalities
PMC - PMC3820267
EDAT- 2013/10/01 06:00
MHDA- 2014/06/18 06:00
PMCR- 2013/11/01
CRDT- 2013/10/01 06:00
PHST- 2013/10/01 06:00 [entrez]
PHST- 2013/10/01 06:00 [pubmed]
PHST- 2014/06/18 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - dmm.012849 [pii]
AID - 0061448 [pii]
AID - 10.1242/dmm.012849 [doi]
PST - ppublish
SO  - Dis Model Mech. 2013 Nov;6(6):1448-58. doi: 10.1242/dmm.012849. Epub 2013 Sep 25.