Analysis Tools
growth/size/body
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• untreated adult homozygotes weigh slightly less than wild-type (by 9% female and 12% male) but appear otherwise grossly normal with skeletal muscle masses similar to those of wild-type controls
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reproductive system
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• male homozygotes are subfertile
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behavior/neurological
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• after 7 days of dexamethasone (DEX) treatment, homozygotes exhibit increased hindlimb grip strength relative to wild-type controls
• however, baseline grip strength is normal
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muscle
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• untreated homozygotes exhibit a lower baseline average cross-sectional area of myofibers in TA muscles relative to wild-type controls
• after 7 days of DEX treatment, homozygotes show no significant decrease in TA myofiber size, unlike wild-type controls
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• on day 7 after DEX treatment, adult female homozygotes show ~40 and ~15% less muscle wasting (atrophy) in tibialis anterior (TA) and gastrocnemius muscle, respectively, relative to DEX-treated wild-type females; male homozygotes show 73% less atrophy in TA and 45% in gastrocnemius relative to DEX-treated wild-type males
• normalizing muscle masses for differences in body weight or body length confirmed protection from DEX-induced atrophy
• after 7 days of DEX treatment, average TA myofiber cross-sectional area is preserved, unlike in DEX-treated wild-type controls
• after 14 days of DEX treatment, marked sparing of muscle loss is also noted in the predominantly fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles
• differences in muscle size between DEX-treated homozygotes and wild-type controls are not due to differences in caloric intake or weight loss
• at 7 days after sciatic nerve denervation, homozygotes show significant sparing of muscle loss (27% in gastrocnemius and 34% in TA), with less atrophy noted in both type I (slow-twitch) and type IIb (fast-twitch) fibers, but not in type IIa fibers, relative to denervated wild-type controls
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homeostasis/metabolism
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• after 7 days of DEX treatment or sciatic nerve denervation, homozygotes show reduced expression of autophagy genes in gastrocnemius and TA muscles relative to wild-type controls
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• after DEX treatment, homozygotes show a similar decrease in the rate of TA myofibrillar and sarcoplasmic protein synthesis relative to wild-type controls, suggesting that sparing of muscle atrophy is likely due to suppressed protein degradation
• after 7 days of DEX treatment or sciatic nerve denervation, homozygotes show reduced expression of select ubiquitin ligases (markers of active muscle wasting) as well as autophagy genes in gastrocnemius and TA muscles relative to wild-type controls
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cellular
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• after 7 days of DEX treatment or sciatic nerve denervation, homozygotes show reduced expression of autophagy genes in gastrocnemius and TA muscles relative to wild-type controls
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