mortality/aging
• less than expected heterozygotes are born from heterozygous intercrosses (39% instead of 66%) and from crosses between heterozygous and wild-type mice (37% instead of 50%)
• crosses between male or female heterozygotes and wild-type mice revealed that heterozygous lethality is not associated with the production of dysfunctional spermatozoa or oocytes
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growth/size/body
• at 4-6 months of age, heterozygotes show decreased lean body mass
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muscle
• at 4 months of age, skeletal muscles of heterozygous mice show a reduction of muscle fiber size (tibialis, -21%; gastrocnemius, -24%; soleus, -26%; EDL, -17%)
• however, total fiber number and fiber type remain unaffected
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• adult heterozygotes show reduced skeletal muscle mass; EDL, tibialis, quadriceps, gastrocnemius and soleus muscle mass is reduced by 14-18% relative to that in wild-type controls
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• during hindlimb immobilization, heterozygotes show an exacerbated immobilization-induced skeletal muscle atrophy associated with reduced protein synthesis and reduced phosphorylation of S6K1 and S6 proteins relative to wild-type controls
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• skeletal muscles of heterozygous mice show a deficiency in polysome content, a reduction in protein synthesis rate and an inhibition of the mechanistic target of rapamycin (MTOR) pathway
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homeostasis/metabolism
• decreased skeletal muscle mass is associated with a reduction in the protein synthesis rate and an inhibition of the MTORC1 pathway
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cellular
• decreased skeletal muscle mass is associated with a reduction in the protein synthesis rate and an inhibition of the MTORC1 pathway
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