Phenotypes Associated with This Genotype

Genotype
MGI:6716017

• Allelic Composition: Fus^tm1Ics/Fus⁺
• Genetic Background: involves: C57BL/6

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

behavior/neurological

abnormal gait ( J:371167 )

♂ • mice show irregular walking pattern characterized by phases of fast walking interrupted with stance phases

♂ • mice show impaired swing and body speed at 22 months of age

short stride length ( J:371167 )

♂ • reduction in hind limb stride length associated with an increase in body speed variation at 10 and 22 months of age

cellular

increased oligodendrocyte number ( J:371167 )

♂ • oligodendrocytes are more numerous in ventral horn white matter in 22-month-old mice

muscle

abnormal muscle electrophysiology ( J:371167 )

♂ • 22-month-old mice show typical fibrillation and fasciculation potentials in gastrocnemius and tibialis anterior muscle indicating the presence of spontaneous denervation activities

♂ • electromyography shows increased frequency of abnormal potentials in gastrocnemius and tibialis anterior muscle at 22, but not 10, months of age and the amplitude of compound muscle action potentials is decreased in 18- to 22- month-old mice

muscle weakness ( J:371167 )

♂ • mice show shorter hanging time and decreased holding impulse (represents the total sustained force exerted by the mouse to oppose the gravitational force) in an inverted grid test at 10 and 22 months of age

♂ • however, mice show normal grip strength in the grip test and performance on the rotarod and do not develop paralysis

nervous system

increased oligodendrocyte number ( J:371167 )

♂ • oligodendrocytes are more numerous in ventral horn white matter in 22-month-old mice

abnormal motor neuron morphology ( J:371167 )

♂ • motor neurons exhibit cytoplasmic accumulation of methylated FUS and ubiquitin pathology but no large FUS aggregates

♂ • motor neuron axons in ventral roots show a distribution shifted towards smaller caliber in 22-month-old mice

motor neuron degeneration ( J:371167 )

♂ • degeneration of motor neurons in the lumbar spinal cord is seen at 22 months, but not 10 months of age, with an approximate 30% reduction in number of motor neurons, indicating progressive degeneration

abnormal myelination ( J:371167 )

♂ • mice at 22 months of age show a defect in myelination of motor axons, with a modest decrease in g-ratio for ventral root axons of smaller calibers

♂ • fewer axons show normal myelination in ventral roots

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 6		DOID:0060198	OMIM:608030	J:371167