Phenotypes Associated with This Genotype

Genotype
MGI:5577182

• Allelic Composition: Tg(Thy1-FUS*)19Vlb/0
• Genetic Background: B6.Cg-Tg(Thy1-FUS*)19Vlb

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

mortality/aging

premature death ( J:203550 )

• mice do not survive past 5 months of age

• after developing the first signs of unstable gait, mice reach the terminal stage of disease within a maximum of 2 weeks

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:203550 )

• at around 2.5-4.5 months of age, mice abruptly develop severe motor dysfunction

impaired righting response ( J:203550 )

• lose righting reflex and the ability to move freely within several days of onset

abnormal gait ( J:203550 )

• impaired gait caused by asymmetrical pareses and eventual complete paralysis of limbs

paralysis ( J:203550 )

• mice first show paresis and eventually complete paralysis of limbs

nervous system

microgliosis ( J:203550 )

• rapidly developing muscle paralysis and muscle atrophy

astrocytosis ( J:203550 )

• rapidly developing muscle paralysis and muscle atrophy

motor neuron degeneration ( J:203550 )

• loss of spinal motor neurons

• at the symptomatic stage, mice lose approximately half of their spinal motor neurons and the remaining neurons are shrunken and/or chromatolytic

• selective loss of lower motor neuron populations in the brainstem, including in the motor trigeminal, hypoglossal, and facial nuclei but not in the nucleus abducens

neuronal cytoplasmic inclusions ( J:203550 )

• FUS-positive inclusions are seen primarily in the lower motor neuron cell bodies, axons and, in a subset of cells, in the nucleus

• inclusions are also seen in other neurons throughout the nervous system, including upper motor neurons in the motor cortex

• large eosinophilic inclusions are occasionally seen in the spinal cord

• both cytoplasmic and nuclear inclusions in neurons are resistant to proteinase K treatment, however they are not stained by amyloid-detecting dyes Congo Red or thioflavin S

• ubiquitin-positive inclusions of various sizes and morphology are often observed in motor neurons

• however, only a fraction of FUS-positive inclusions are ubiquitinated

neuronal intranuclear inclusions ( J:203550 )

• FUS-positive inclusions are seen primarily in the lower motor neuron cell bodies, axons and, in a subset of cells, in the nucleus

• both cytoplasmic and nuclear inclusions in neurons are resistant to proteinase K treatment, however they are not stained by amyloid-detecting dyes Congo Red or thioflavin S

peripheral nervous system degeneration ( J:203550 )

• loss of peripheral nerve fibers

• significant neuronal loss and damage of myelinated fibers in peripheral nerves is only seen at the late, generalized stage of the disease

homeostasis/metabolism

dehydration ( J:203550 )

• mice become dehydrated

immune system

microgliosis ( J:203550 )

• rapidly developing muscle paralysis and muscle atrophy

muscle

muscular atrophy ( J:203550 )

• rapidly developing muscle paralysis and muscle atrophy

hematopoietic system

microgliosis ( J:203550 )

• rapidly developing muscle paralysis and muscle atrophy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 6		DOID:0060198	OMIM:608030	J:203550