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Table 3 Knockout and knock-in models of IGF1-Akt pathway components: effect on growth

From: Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models

Genotype1 Viability Growth phenotype References
Igf1 null Severe neonatal lethality Severe growth retardation [3739]
Igf1 null in muscle (Mef2c-Cre) Viable Normal growth [63]
Igf1 receptor null Severe neonatal lethality Severe growth retardation [37, 39]
Igf1 receptor null in muscle (Mef2c-Cre) Viable Reduced body weight, reduced muscle fiber number and size [63]
IRS1 null Viable Reduced growth (weight 30-60% of control) [64, 122]
IRS2 null Viable Almost normal growth (birth weight 90% of control) [65]
PI3K p85α + p55α + p50α null Perinatal lethality   [66]
PI3K p85α + p55α + p50α null in heart & muscle (MCK-Cre) Viable Normal growth [68]
PI3K p85β null Viable Normal growth [67]
PI3K p85α + p55α + p50α null in heart & muscle (MCK-Cre) and p85β null Viable Reduced heart size but not muscle size [68]
PTEN null in heart & muscle (MCK-Cre) Viable Cardiac hypertrophy but normal skeletal muscle growth; unaffected overload-induced muscle hypertrophy; improved muscle regeneration [70, 71, 123]
PDK1 null Embryonic lethality   [124]
PDK1 knock-in mutant unable to bind phosphoinositides Viable Reduced growth (weight 35% of control) [125]
PDK1 null in heart & muscle (MCK-Cre) Lethal at 5-11 weeks Dilated cardiomyopathy but no change in muscle [73]
Akt1 null Viable but shorter life span Mild growth retardation (weight 80% of control) [74, 75]
Akt2 null Viable Normal growth [76]
Akt1+Akt2 null Neonatal lethality Severe growth retardation (birth weight 50% of control), marked muscle atrophy [77]
TSC1 null Embryonic lethality   [126]
TSC2 null Embryonic lethality   [127]
mTOR null Embryonic lethality   [128, 129]
mTOR null in muscle (HSA-Cre) Viable but premature death Reduced postnatal growth due to reduced fast muscle growth, severe myopathy [88]
Raptor null Embryonic lethality   [6]
Raptor null in muscle (HSA-Cre) Viable Normal growth [87]
Rictor null in muscle (HSA-Cre) Viable Reduced postnatal growth with severe myopathy and premature death [87]
S6K1 null Viable Reduced growth (birth weight 80% of control), reduced muscle growth (fiber size 80% of control in adult mice) [89, 117]
S6K2 null Viable Normal growth [130]
S6K1+S6K2 null Perinatal lethality Reduced growth [130]
4EBP1+4EBP2 null Viable Normal growth [131]
FoxO1 null Embryonic lethality   [132, 133]
FoxO1 null in muscle (HSA-Cre) Viable Normal growth, slow to fast switch in muscle [134, 135]
FoxO3 null Viable but female sterility Normal growth [133, 36]
FoxO4 null Viable Normal growth [137]
FoxO3+FoxO4 null Viable Normal growth [137]
MAFbx null Viable Reduced muscle atrophy after denervation [92]
Murf1 null Viable Reduced muscle atrophy after denervation [92]
  1. 1 Promoters used to drive Cre recombinase expression: HSA = human skeletal actin; MCK = muscle creatine kinase; Mef2c = a promoter that lies 71 kb upstream of the first translated exon of the Mef2c gene and is sufficient to direct expression exclusively to skeletal muscle from embryonic day 8.5.