mortality/aging
• death occurs by 7 weeks post-induction by doxycycline treatment
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growth/size/body
weight loss
(
J:132185
)
• after transgene induction by doxycycline, mice display significant weight loss by 2 weeks post-induction; by 4 weeks, phenotypic difference in body mass is clear compared to wild-type littermates
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muscle
• degenerating myofibers in treated mice show loss of myofibrillar pattern, mitochondrial swelling and dilated tubular structures
• extensive fiber regeneration is observed with half the fibers being centrally nucleated
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• doxycycline-treated animals show significant variability in myofiber size (triceps brachii, tibialis anterior and vastus lateralis) with numerous small caliber fibers with round shape and multifocal clusters of mononuclear cells; small fibers are most marked within vastus lateralis muscle
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• many fibers of small and large caliber contain internal nuclei
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• weight of each individual muscle is decreased (including triceps, tibialis anterior, and most markedly vastus lateralis)
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• docycycline-treated animals exhibit myodegeneration indicated by myonecrosis and phagocytosis
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behavior/neurological
• by 5-6 weeks post-induction by doxycycline treatment, animals display pelvic limb weakness
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• by 5-6 weeks post-induction by doxycycline treatment, phenotype is more severe, with animals show decreased activity
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skeleton
• by 4 weeks post-induction by doxycycline treatment, mice display visible kyphosis
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homeostasis/metabolism
• after 6 weeks of doxycycline treatment, animals have elevated serum creatine kinase activity, consistent with myodegeneration, but controls do not
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