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Table I.

Evidence for the role of NFAT isoforms in the development of numerous cell types


Tissue/cell type

NFAT isoform implicated

Methods used to determine role for NFAT

Target gene

Function

References
Heart NFATC1 NFATC1−/− mice Development of heart valve de la Pompa et al., 1998; Ranger et al., 1998  
Vascular endothelial cells (primary cells) NFATC2 EMSA and reporter assays1; PG rescue of CSA effect in vitro/in vivo COX2 VEGF signaling;
 PG synthesis during angiogenesis Armesilla et al., 1999; Hernandez et al., 2001  
Perivascular tissue NFATC3/C4 NFATC3/C4 double
 null mice Organization of developing blood vessels Graef et al., 2001a  
Skeletal muscle
 reserve cells NFATC1 Overexpression and inhibition of NFAT in primary muscle cultures myf-5 Expression of myf5 Friday and Pavlath, 2001  
Skeletal muscle myotubes NFATC2 NFATC2−/− mice Skeletal muscle growth Horsley et al., 2001  
Skeletal muscle myoblasts NFATC3 NFATC3−/− mice Formation of primary myofibers Kegley et al., 2001  
Chondrocytes NFATC2 NFATC2−/− mice Inhibition of chondrogenesis Ranger et al., 2000  
Keratinocytes
 (primary cells)
 
NFATC3
 
Reporter assays2; NFAT inhibition; CSA treatment
 
p21WAF1/CIP
 
Activation of p21
 during differentiation
 
Santini et al., 2001 
 
Adipocytes (cell line)
 
NFATC2/C4
 
EMSA and reporter assays3; CSA treatment
 
aP2
 
Expression of adipocyte specific genes during differentiation
 
Ho et al., 1998 
 

Tissue/cell type

NFAT isoform implicated

Methods used to determine role for NFAT

Target gene

Function

References
Heart NFATC1 NFATC1−/− mice Development of heart valve de la Pompa et al., 1998; Ranger et al., 1998  
Vascular endothelial cells (primary cells) NFATC2 EMSA and reporter assays1; PG rescue of CSA effect in vitro/in vivo COX2 VEGF signaling;
 PG synthesis during angiogenesis Armesilla et al., 1999; Hernandez et al., 2001  
Perivascular tissue NFATC3/C4 NFATC3/C4 double
 null mice Organization of developing blood vessels Graef et al., 2001a  
Skeletal muscle
 reserve cells NFATC1 Overexpression and inhibition of NFAT in primary muscle cultures myf-5 Expression of myf5 Friday and Pavlath, 2001  
Skeletal muscle myotubes NFATC2 NFATC2−/− mice Skeletal muscle growth Horsley et al., 2001  
Skeletal muscle myoblasts NFATC3 NFATC3−/− mice Formation of primary myofibers Kegley et al., 2001  
Chondrocytes NFATC2 NFATC2−/− mice Inhibition of chondrogenesis Ranger et al., 2000  
Keratinocytes
 (primary cells)
 
NFATC3
 
Reporter assays2; NFAT inhibition; CSA treatment
 
p21WAF1/CIP
 
Activation of p21
 during differentiation
 
Santini et al., 2001 
 
Adipocytes (cell line)
 
NFATC2/C4
 
EMSA and reporter assays3; CSA treatment
 
aP2
 
Expression of adipocyte specific genes during differentiation
 
Ho et al., 1998 
 
1

COX2 promoter construct.

2

NFAT reporter and p21 promoter constructs.

3

aP2 promoter construct.

PG, prostaglandin.

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