Phenotypes Associated with This Genotype

Genotype
MGI:3783326

• Allelic Composition: Tg(CAG-rtTA)72Wiek/0; Tg(tetO-Rnf5)1Zron/0
• Genetic Background: involves: C3H * C57BL/6 * DBA/2

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:132185 )

• death occurs by 7 weeks post-induction by doxycycline treatment

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

muscle

abnormal skeletal muscle fiber morphology ( J:132185 )

• 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

increased variability of skeletal muscle fiber size ( J:132185 )

• 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

centrally nucleated skeletal muscle fibers ( J:132185 )

• many fibers of small and large caliber contain internal nuclei

decreased skeletal muscle weight ( J:132185 )

• weight of each individual muscle is decreased (including triceps, tibialis anterior, and most markedly vastus lateralis)

muscle degeneration ( J:132185 )

• docycycline-treated animals exhibit myodegeneration indicated by myonecrosis and phagocytosis

behavior/neurological

weakness ( J:132185 )

• by 5-6 weeks post-induction by doxycycline treatment, animals display pelvic limb weakness

decreased locomotor activity ( J:132185 )

• by 5-6 weeks post-induction by doxycycline treatment, phenotype is more severe, with animals show decreased activity

skeleton

kyphosis ( J:132185 )

• by 4 weeks post-induction by doxycycline treatment, mice display visible kyphosis

homeostasis/metabolism

increased circulating creatine kinase level ( J:132185 )

• after 6 weeks of doxycycline treatment, animals have elevated serum creatine kinase activity, consistent with myodegeneration, but controls do not