Phenotypes Associated with This Genotype

Genotype
MGI:5500068

• Allelic Composition: Vcp^tm1Itl/Vcp^tm1Itl
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

postnatal lethality, complete penetrance ( J:191963 )

• lethality is seen from birth to 21 days of age

growth/size/body

decreased body size ( J:191963 )

• small at birth and remain small

decreased body weight ( J:191963 )

postnatal growth retardation ( J:191963 )

• severe

behavior/neurological

decreased grip strength ( J:191963 )

• mutants are unable to complete the grip strength test due to severe muscle weakness

muscle

abnormal sarcomere morphology ( J:191963 )

• quadriceps muscles show abnormal sarcomeric architecture

abnormal skeletal muscle morphology ( J:191963 )

• increase in endomysial space

• quadriceps muscles show abnormal mitochondrial proliferation with large megaconia and disrupted cristae

abnormal skeletal muscle fiber morphology ( J:191963 )

• 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

skeletal muscle fiber necrosis ( J:191963 )

increased variability of skeletal muscle fiber size ( J:191963 )

• wide variation in fiber size

centrally nucleated skeletal muscle fibers ( J:191963 )

decreased skeletal muscle mass ( J:191963 )

skeletal muscle endomysial fibrosis ( J:191963 )

muscle weakness ( J:191963 )

• poor mobility due to muscle weakness

myopathy ( J:191963 )

• 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

abnormal heart morphology ( J:191963 )

• 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

abnormal mitochondrial crista morphology ( J:191963 )

• mitochondrial cristae are disrupted in quadriceps muscles

abnormal autophagy ( J:191963 )

• in muscle tissue

skeletal muscle fiber necrosis ( J:191963 )

increased mitochondrial fission ( J:191963 )

• quadriceps muscles show abnormal mitochondrial proliferation

integument

focal hair loss ( J:191963 )

• hairless patches of skin resembling ichthyosis-like thickening

limbs/digits/tail

abnormal limb bone morphology ( J:191963 )

• non-symmetrical Paget-like bone lesions of the right hind limb bone

nervous system

abnormal brain morphology ( J:191963 )

• 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

gliosis ( J:191963 )

• increase in GFAP staining suggesting gliosis

motor neuron degeneration ( J:191963 )

• rapid motor neuron degeneration in spinal cords

skeleton

abnormal limb bone morphology ( J:191963 )

• non-symmetrical Paget-like bone lesions of the right hind limb bone

kyphosis ( J:191963 )

homeostasis/metabolism

abnormal autophagy ( J:191963 )

• 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