Phenotypes Associated with This Genotype

Genotype
MGI:3698861

• Allelic Composition: Gne^tm1Sngi/Gne^tm1Sngi; Tg(ACTB-GNE*D176V)9Sngi/0
• Genetic Background: involves: C57BL/6

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

mortality/aging

premature death ( J:117854 )

• lower median survival rate

muscle

abnormal myocardium layer morphology ( J:117854 )

• about 20% of mice develop fibrosis in the cardiac muscle after 30 weeks of age and some cardiomyocytes show amyloid deposition and rimmed vacuoles

abnormal skeletal muscle morphology ( J:117854 )

• 5 of 12 mice that died displayed rimmed vacuoles in the skeletal muscles

• muscle cross sections are positive for Congo red stained protein deposits and about 62% of rimmed vesicles contain amyloid proteins

• accumulation of these proteins starts at 32 to 34 weeks of age

abnormal skeletal muscle fiber morphology ( J:117854 )

• after 40 weeks of age, rimmed vacuoless and occasional inclusion bodies are seen in scattered fibers

skeletal muscle fiber atrophy ( J:117854 )

• some fibers appear atrophic by 40 weeks of age

increased variability of skeletal muscle fiber size ( J:117854 )

• increase in variation of fiber size with age that preferentially affects the gastrocnemius and quadriceps muscles

abnormal diaphragm morphology ( J:117854 )

• 3 of 12 mice had fibrosis and a few rimmed vacuoles in the diaphragm

muscular atrophy ( J:117854 )

• some muscles, particularly the gastrocnemius, are atrophic

abnormal muscle physiology ( J:117854 )

• vacuolated muscle fibers shows signs of the unfolded protein response and activation of autophagy

muscle weakness ( J:117854 )

• reduced muscle strength noted after 30 weeks of age

growth/size/body

decreased body weight ( J:117854 )

• after 30 weeks of age, mice weigh significantly less than control littermates

• lower body weight is more pronounced and develops earlier in females compred to males

homeostasis/metabolism

increased circulating creatine kinase level ( J:117854 )

• elevated serum creatine kinase activity compared to littermate controls starting at 30 weeks of age

cardiovascular system

abnormal myocardium layer morphology ( J:117854 )

• about 20% of mice develop fibrosis in the cardiac muscle after 30 weeks of age and some cardiomyocytes show amyloid deposition and rimmed vacuoles

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inclusion body myositis		DOID:3429	OMIM:147421	J:117854