Phenotypes Associated with This Genotype

Genotype
MGI:5644693

• Allelic Composition: Meox2^tm1(cre)Sor/Meox2⁺; Tg(CAG-lacZ,-FUS*R521G,-EGFP)682Gyu/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

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

Tg(CAG-lacZ,-FUS*R521G,-EGFP)682Gyu/0 Meox2^tm1(cre)Sor/Meox2⁺ mice display hindlimb curl

mortality/aging

premature death ( J:216672 )

• about 50% of mice die before P30

growth/size/body

decreased body weight ( J:216672 )

• mice that survive past P30 exhibit reduced body mass

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:216672 )

• mice that survive past P30 display a subtle motor impairment

impaired righting response ( J:216672 )

• mice exhibit reduced righting ability, however to a lesser extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice

limb grasping ( J:216672 )

• mice exhibit hindlimb clasping, but to a lesser extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice

impaired coordination ( J:216672 )

• on the rotarod, mice that escape early lethality show normal performance on day 1 of testing, however show impaired motor function on day 2 of testing

decreased grip strength ( J:216672 )

• mice exhibit reduced grip strength, however to a lesser extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice

abnormal gait ( J:216672 )

• mice develop gait abnormalities that are less severe than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice

• gait analysis of mice that escape early lethality shows that the braking phase is greater in the forelimbs and the swing phase is reduced in the hindlimbs

• in the ladder-walking test, the forelimbs of mice that escape early lethality have more errors in stepping with few deficits in the hindlimbs

decreased locomotor activity ( J:216672 )

• mice that escape early lethality show less activity over a 9-day period on voluntary running wheels

• however, food intake is not altered

abnormal social investigation ( J:216672 )

• interaction with juvenile mice is reduced at 4 months of age

• when introduced to intruder adult mice, mutants do not show any deficits before 8 months of age, at which time they show reduced chasing behavior

muscle

muscular atrophy ( J:216672 )

• end-stage mutants exhibit scattered and grouped atrophic muscle fibers, although to a lower extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice

nervous system

microgliosis ( J:216672 )

• mice that die by P30 exhibit activation of microglia in the brain and spinal cord

• however, mice that escape early lethality do not exhibit microglial and astrocyte activation in the brain and spinal cord

• mice also do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords

astrocytosis ( J:216672 )

• mice that die by P30 exhibit activation of astrocytes in the brain and spinal cord

abnormal dendrite morphology ( J:216672 )

• dendritic intersections and cumulative area of dendrites are reduced in spinal motor neurons at P18 and these deficits are significant and persistent at P60

• fewer intersections and reduced cumulative area in the apical and basal dendrites in neurons of sensorimotor cortex layers IV-V at P18 and P60

abnormal dendritic spine morphology ( J:216672 )

• decrease in the number and density of mature spines

abnormal neuromuscular synapse morphology ( J:216672 )

• end-stage mutants show abnormalities and degeneration of neuromuscular junctions

hematopoietic system

microgliosis ( J:216672 )

• mice that die by P30 exhibit activation of microglia in the brain and spinal cord

• however, mice that escape early lethality do not exhibit microglial and astrocyte activation in the brain and spinal cord

• mice also do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords

immune system

microgliosis ( J:216672 )

• mice that die by P30 exhibit activation of microglia in the brain and spinal cord

• however, mice that escape early lethality do not exhibit microglial and astrocyte activation in the brain and spinal cord

• mice also do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords

taste/olfaction

taste/olfaction phenotype ( J:216672 )

N • mice exhibit normal olfaction and cognitive function

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 6		DOID:0060198	OMIM:608030	J:216672