Table 2.

Phenotypes of mouse models and human conditions with modified STAT3 signaling.

Model	Effect on STAT3	Phenotype	References
Stat3−/−	STAT3 deletion in all cells	Early embryonic death (day E8.5).	50
Hyperimmunoglobulinemia E (hyper-IgE) syndrome (human)	STAT3-DNA binding reduced in all cells	Low bone mineral density, recurrent fractures, craniofacial abnormalities.	58
SA/SA and SA/ −	Reduced STAT3 phosphorylation in all cells	SA/SA phenotypically normal; lower STAT3 phosphorylation in SA/−, associated with 75% perinatal lethality and reduced skeletal size.	54
Dmp1Cre.Stat3fl/fl	STAT3 deletion in osteocytes	Low bone mass owing to impaired bone formation; reduced bone formation response to mechanical loading.	73
Col1α1(2.3 kb) Cre; Stat3flox/flox	STAT3 deletion in osteoblasts and osteocytes	Low trabecular bone mass owing to reduced bone formation; normal bone length; reduced bone formation response to mechanical loading.	68,76
Col1α1(3.6 kb) Cre; Stat3flox/flox	STAT3 deletion in chondrocytes, osteoblasts, and osteocytes	Very small skeletal size; low trabecular bone mass owing to reduced bone formation and increased osteoclast formation.	76
Prrx1Cre; Stat3flox/flox	STAT3 deletion in chondrocytes, osteoblasts, and osteocytes	Reduced skeletal size and postnatal limb curvature; no data on bone mass.	55
TCre.Stat3f/f	STAT3 deletion in mesoderm-derived cells	Shortened limbs at birth and limb curvature in postnatal development; no data on bone mass.	55
Tie2(Tek)Cre.Stat3f/f	STAT3 deletion in endothelial and hematopoietic cells	Reduced skeletal size and bone mass owing to impaired bone formation and increased resorption; secondary to inflammatory colitis.	81
Socs3−/−	SOCS3 deletion; elevated STAT3 signaling in all cells	Embryonic lethality.	84,85
VavCre.Socs3f/f	Elevated STAT3 signaling in endothelial and hematopoietic cells	Joint inflammation, low bone mass owing to increased osteoclast formation both in joints and systemically; increased osteoblast formation.	86
Dmp1Cre.Socs3f/f	Elevated STAT3 signaling in osteocytes	Increased cortical porosity owing to delayed development of cortical bone, particularly in females; elevated bone formation and increased resorption later in life.	87
Dmp1Cre.Socs3f/f.IL-6−/−	Elevated STAT3 signaling in osteocytes but not downstream of IL-6	Increased cortical porosity owing to delayed development of cortical bone in males and females.	87
Dmp1Cre.Socs3f/f.Il6st f/f	Elevated STAT3 signaling in osteocytes but not downstream of gp130	Rescue of the Dmp1Cre.Socs3f/f phenotype.	91
Col2Cre.Socs3f/f	Elevated STAT3 signaling in chondrocytes, osteoblasts and osteocytes	Increased cortical porosity, and reduced bone size.	89