Table 1. Mouse models of TGF-β/BMP signaling in bone.

Classification	Gene	KO/CKO/Tg	Defects	Reference
TGF-β ligands and receptors	Tgfb1	KO	Die at 1 month, normal skeleton	25
		Tgfb1–/–Rag2–/–	Evade early death, lower bone density	8
		Col1 promoter; CA-TGFβ1 Tg	Defects resembling Camurati–Engelmann disease, osteoarthritis	8,37
	Tgfb1/ Tgfb2	DKO	Lack of distal parts of the rib	251
	Tgfb2	KO	Defects in both intramembranous bone and endochondral bone, craniofacial defects	24
	Tgfb3	KO	Normal skeleton, palate cleft	27
	Tgfbr2	Col2-Cre	Defects in the skull base and vertebrae, normal long bone	47
		Prx1-Cre	Short limbs and phalange joint fusion	44–46
		Ocn-Cre	Increase bone mass	43
		nestin–CreTM	Less-developed osteoarthritis	37
		MTII promoter; DN-TβRII Tg	Bifurcation of the xiphoid process and sternum, automatic osteoarthritis	34
		Dermo1-Cre	Short and wide long bone, joint fusion, ectopic chondrocyte protrusion, reduced bone density	30
	Alk5	KO	Increase bone mass, decreased bone turn over, reduced body size, early ossification of the skull base	39
BMP ligands and receptors	Bmp2	Col2-Cre	Chondrodysplasia	86
		KO	Newborn death, skeletal patterning defects restricted to the rib cage, the skull, and the hindlimbs	80
	Bmp7	Prx1-Cre	Normal bone and no defects in fracture healing, progressive osteoarthritis	70
		Prx1-Cre	Mild defects in skeletogenesis, normal osteogenesis	82
	Bmp2/7	Prx1-Cre	Normal bone and no defects in fracture healing	84
	Bmp4	Prx1-Cre	Impairment of osteogenesis, malformed limbs	82
	Bmp2/4	Col2-Cre	Chondrodysplasia	86
	BMP-2/-4/-7	KO	More trabecular bone	72
	Bmp3	Tg	Less bone, defected bone collar, spontaneous rib fracture	73
		KO	Phalangeal defects	77,109
	Bmpr1b	Col1 promoter; DN-BMPRII Tg	Reduced bone, delayed calvarial and vertebrae mineralization	94
		Col2-Cre	Chondrodysplasia, shortened bone, delayed ossification	104,110
	Bmpr1a	Ocn-Cre	Low bone mass, low bone turnover	95
		Col1-Cre;ERTM	Increase bone mass, more bone resorption, less OB	96–98
		Gdf5-Cre	Articular cartilage wears	89
	Acvr1	Col2-Cre	Defected skull and cervical vertebrae, progressive kyphosis	105,252
		CA-ALK2 Tg	Ectopic ossification resembling FOP	90
	Bmpr1a/ Bmpr1b	Col2-Cre	Absent skeleton elements formed through endochondral ossification	104,110
	Acvr1/ Bmpr1a	Col2-Cre	generalized perinatal lethal chondrodysplasia	105
	Acvr1/ Bmpr1b	Col2-Cre	generalized perinatal lethal chondrodysplasia	105
Smad pathway	Smad1	Col2-Cre	Defected calvarial bone development, shortening of growth plate	113,114
		Col1-Cre	osteopenia	113
	Smad2	KO	severe craniofacial defects	253
	Smad1/Smad5	Col2-Cre	Severe chondrodysplasia	115
	Smad3	KO	Osteopenia, accelerated chondrocyte hypertrophy, osteoarthritis	52
		Col2-Cre	progressive osteoarthritis	58
	Smad4	Col2-Cre	Dwarfism, disorganized growth plate, ectopic bone collars	120
		Ocn-Cre	Lower bone mass <6-month, more trabecular bone >7-month	121
		Osx-Cre	Stunted growth, spontaneous fracture, Osteogenesis imperfecta, CCD, Wnt-deficiency symdrome	122
		Osx-Cre	Increase mitosis, decrease differentiation & mineralization of OB	123
Non-Smad pathway	TAK1	Osx-Cre	Clavicular hypoplasia and delayed fontanelle fusion	127
		Col2-Cre	Cartilage defects, failure to maintain interzone cells of the elbow joint	125
		Prx1-Cre	Cartilage defects, widespread joint fusions	125
Other regulators	Smad6	Col2 promoter; Tg	Dwarfism, osteopenia, delayed chondrocyte hypertrophy	162
	Smad6/Smurf1	Col2 promoter; Tg	Severely delayed endochondral bone formation	162
	Smad7	Prx1 promoter; Tg	Impede condensation, poor cartilage formation	165
	Smurf1	KO	Age-dependent increase of bone mass	167
	Tob	KO	High bone mass	174,175
	Ltbp-3	Prx1-Cre	Normal bone but spontaneous fracture	83
	Nog	KO	Malformed skeleton, rescued by reduction of Bmp4 dosage	138,139
		Ocn promoter; Tg	Osteopenia	142,143
	Nog/Grem1	DKO	No sclerotome	140
	Nog/Follistatin	DKO	No sclerotome, trunk cartilage formation	141
	Nog/Chordin	Chordin–/–Nog+/–	Head defects	155

BMP, bone morphogenetic protein; TGF-β, transforming growth factor-β.