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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.