Perturbations in Insulin/IGF-1 signaling resulting in diminished skeletogenesis
Gene(s) modifed1 Genetic approach2 Phenotype Ref.
Dwarf Trabecular Bone Cortical Bone BMD Bone
Strength
Gab1 C (OC-Cre) NR3 NR 24
IRS1 G Yes NR 26
IRS2 G No NR 25
Akt1 G Yes NR 29
Akt1 & Akt2 G Yes NR NR NR NR 28
FoxO1 C (Col1a1-Cre) No NR 32
FoxO1, 3 & 4 MT (Mx-Cre) No NR 33
IGF1R C (OC-Cre) No NR 44
IGF1R C (Osx-Cre) Yes NR NR NR 45
IR C (Col1a1-Cre) NR NR NR NR 59
IR C (OC-Cre) NR NR NR NR 57
MEK1 TG (dominant/negative) Yes NR NR NR 38
Perturbations in Insulin/IGF-1 signaling resulting in enhanced skeletogenesis
MEK1 TG
(active )
No
(large)
NR NR NR 38
PTEN C (OC-Cre) NR NR 30
FoxO1, 3 & 4 C (Osx-Cre) NR NR NR 34
1 Pathways presented in Figure 1.
2Genetic Approach: C= conditional knockout; G=global knockout; MT = multiple tissue knockout; TG = transgenic over-expression.
3NR = Not reported
Table 1: Various mouse models in which components of insulin and/or IGF-I signaling have been independently assessed in skeletogenesis.