Phenotypes Associated with This Genotype

Genotype
MGI:4849542

• Allelic Composition: Vcp^tm1Itl/Vcp⁺
• Genetic Background: B6.129S-Vcp^tm1Itl

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

muscle

abnormal skeletal muscle fiber morphology ( J:166230 )

• beginning at 9 months, myofibrils exhibit vacuoles unlike in wild-type mice

• at 15 months, myofibrils contain more vacuoles than wild-type cells

• myofibrils exhibit disorganized sarcomere and swelling of mitochondria unlike in wild-type mice

• myofibrils exhibit Tardbp+ (TDP-43) and ubiquitin+ cytoplasmic inclusion bodies unlike in wild-type mice

increased variability of skeletal muscle fiber size ( J:166230 )

centrally nucleated skeletal muscle fibers ( J:166230 )

• at 9 to 10 months and 15 months

progressive muscle weakness ( J:166230 )

• at 6 months and worsening with age, as determined by performance on a rotarod and grip strength test

myopathy ( J:166230 )

• muscles exhibit increased autophagy and apoptosis compared with wild-type muscles

behavior/neurological

behavior/neurological phenotype ( J:166230 )

N • mice exhibit normal short term memory

impaired coordination ( J:166230 )

• at 3 months and worsening with age on a rotarod

decreased grip strength ( J:166230 )

• at 3 months and worsening with age

seizures ( J:166230 )

• in up to 15% of mice

tonic-clonic seizures ( J:166230 )

skeleton

abnormal osteoclast differentiation ( J:166230 )

• bone marrow derived macrophages form more osteoclasts in culture than wild-type cells

increased osteoclast cell number ( J:166230 )

• mice exhibit increased osteoclasts compared with wild-type mice

• bone marrow derived macrophages form more osteoclasts in culture than wild-type cells

increased compact bone thickness ( J:166230 )

decreased trabecular bone connectivity density ( J:166230 )

• trabecular pattern factor is decreased compared to in wild-type mice

decreased bone mass ( J:166230 )

• mice exhibit radiolucency of distal femurs and proximal tibiae compared with wild-type mice

nervous system

seizures ( J:166230 )

• in up to 15% of mice

tonic-clonic seizures ( J:166230 )

abnormal neuron morphology ( J:166230 )

• at 15 month, neurons in the frontal cortex exhibit a Tardbp+ (TDP-43) and ubiquitin+ inclusions unlike in wild-type mice

immune system

abnormal osteoclast differentiation ( J:166230 )

• bone marrow derived macrophages form more osteoclasts in culture than wild-type cells

increased osteoclast cell number ( J:166230 )

• mice exhibit increased osteoclasts compared with wild-type mice

• bone marrow derived macrophages form more osteoclasts in culture than wild-type cells

cellular

abnormal autophagy ( J:166230 )

• muscle tissue exhibits autophagy unlike in wild-type tissue

abnormal osteoclast differentiation ( J:166230 )

• bone marrow derived macrophages form more osteoclasts in culture than wild-type cells

hematopoietic system

abnormal osteoclast differentiation ( J:166230 )

• bone marrow derived macrophages form more osteoclasts in culture than wild-type cells

increased osteoclast cell number ( J:166230 )

• mice exhibit increased osteoclasts compared with wild-type mice

• bone marrow derived macrophages form more osteoclasts in culture than wild-type cells

homeostasis/metabolism

abnormal autophagy ( J:166230 )

• muscle tissue exhibits autophagy unlike in wild-type 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:166320