mortality/aging
N |
• mice are viable and develop normally
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muscle
N |
• analysis of myofilament structure using sarcomeric alpha-actinin 2 indicated normal sarcomerogenesis in tibialis anterior (TA) muscles
• immunofluorescence analysis of sarcomeric alpha-actinin 2 and titin-M8 localization revealed that Z-disc and M-band structures are not significantly altered
• at 4 months of age, muscle weight to tibia-length ratios for TA, soleus, gastrocnemius and extensor digitorum longus (EDL) muscles are normal
• no significant changes are observed in the number of centralized nuclei in TA muscle at 4 months of age
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• skeletal muscles show a slight decrease in protein levels of utrophin and other dystrophin-sarcoglycan (DSG) components, including alpha-dystrobrevin, whereas levels of tubulin are slightly increased
• although overall dystrophin levels are normal, subsarcolemmal dystrophin localization in longitudinal sections of TA muscles is more patchy and abnormally distributed than in single Obscntm1Chen knockouts, indicating exacerbated membrane fragility
• a significant portion of TA muscle fibers are mouse IgG-positive, unlike in single Obscntm1Chen knockouts or Obsl1 skeletal muscle-knockouts, suggesting impaired sarcolemmal integrity
• increased membrane fragility leads to upregulation of dysferlin and filamin C proteins (involved in muscle repair), reduced caveolin-1 and TRPC1 protein levels, but normal levels of neuronal nitric oxidase (nNOS) and L-type calcium channel DHPR alpha-2 subunit, indicating potential changes to DSG-associated, but not T-tubule-based ion channels
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• TA muscles show a decrease in small ankyrin-1.5 (sAnk1.5) protein levels similar to that in single Obscntm1Chen knockouts
• skeletal muscles show alterations to levels of lumenal SR calcium binding proteins (sarcalumenin and Casq2) as well as sarcoendoplasmic reticulum Ca2+ ATPase (Serca)
• proteome and expression data revealed increases in junctional SR proteins like triadin, junction and ryanodine receptors
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• analysis of cross-sectional areas of TA muscle revealed a decrease in fiber size
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• analysis of twitch parameters in EDL muscles revealed increased time-to-peak (TtP) values relative to control and Obsl1 skeletal muscle-knockouts
• however, half-relaxation times remain normal
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homeostasis/metabolism
• monoamine oxidase A and B levels are significantly decreased in TA muscles
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• catalase levels are significantly increased in soleus muscle
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• muscle glycogen phosphorylase, the rate determining enzyme responsible for glycogen breakdown, is significantly decreased
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cellular
• almost all identified mitochondrial electron transport chain proteins are downregulated in soleus and TA muscles
• analysis of whole TA and/or soleus muscle extracts using oxphos antibody cocktail or a Uqcrb antibody revealed slightly or significantly reduced levels of mitochondrial complex I, II, III, IV, and V proteins
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reproductive system
N |
• mice are fertile
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