mortality/aging
• lethality is seen from birth to 21 days of age
|
growth/size/body
• small at birth and remain small
|
• severe
|
behavior/neurological
• mutants are unable to complete the grip strength test due to severe muscle weakness
|
muscle
• quadriceps muscles show abnormal sarcomeric architecture
|
• increase in endomysial space
• quadriceps muscles show abnormal mitochondrial proliferation with large megaconia and disrupted cristae
|
• increase in the number of internal nucleation and splitting myofibers
• myofibrils contain ubiquitin aggregates and inclusions and small angular muscle fibers contain TDP-43 positive sarcoplasmic inclusions
• infiltration of triglycerides and lipids in quadriceps muscle fibers
|
• wide variation in fiber size
|
• poor mobility due to muscle weakness
|
• myopathic changes in the bilateral tibialis anterior, bilateral hamstrings and bilateral medial gastrocnemius, and unilateral thoracic paraspinal muscles
• muscles show abnormal motor units and myotonic discharge and a reduction in recruitment and interference patterns
• muscles show increased autophagy
|
cardiovascular system
• enlarged vacuoles, dilated vascular channels, and abnormal architecture of the channels in the heart
• however, ventricle wall thickness and mass are normal and function appears normal
|
cellular
• mitochondrial cristae are disrupted in quadriceps muscles
|
• in muscle tissue
|
• quadriceps muscles show abnormal mitochondrial proliferation
|
integument
• hairless patches of skin resembling ichthyosis-like thickening
|
limbs/digits/tail
• non-symmetrical Paget-like bone lesions of the right hind limb bone
|
nervous system
• brain shows absence of well-defined synaptic complexes, post-synaptic enlargement and vesicular degeneration
• perinuclear and cytosolic accumulation of ubiquitin-positive deposits are seen in the brain
|
• rapid motor neuron degeneration in spinal cords
|
skeleton
• non-symmetrical Paget-like bone lesions of the right hind limb bone
|
homeostasis/metabolism
• in muscle tissue
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
inclusion body myopathy with Paget disease of bone and frontotemporal dementia | DOID:0050881 |
OMIM:PS167320 |
J:191963 |