Phenotypes Associated with This Genotype

Genotype
MGI:5445435

• Allelic Composition: Tg(Prnp-FUS)WT3Cshw/Tg(Prnp-FUS)WT3Cshw
• Genetic Background: involves: C57BL/6 * Crl:CD-1(ICR)

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

mortality/aging

premature death ( J:189360 )

• by 10 to 13 weeks (average survival 82 days)

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:189360 )

• from 4 weeks, mice exhibit rapid decline in motor function

limb grasping ( J:189360 )

• by 8 weeks

tremors ( J:189360 )

• at 4 weeks

impaired coordination ( J:189360 )

• from 4 weeks

abnormal gait ( J:189360 )

• slightly stilted at 4 weeks due to hind limb dysfunction

decreased locomotor activity ( J:189360 )

• by 8 weeks, mice travel less distance in an open field compared with wild-type mice

hindlimb paralysis ( J:189360 )

• progressive by 8 weeks

nervous system

microgliosis ( J:189360 )

• in the anterior horn and white matter tracts of the spinal cord

astrocytosis ( J:189360 )

• in the anterior horn of the spinal cord

abnormal neuron morphology ( J:189360 )

• at end-stage, mice exhibit numerous ring-like perinuclear inclusions in layer V neurons of the motor and somatosensory cortices, the insular cortex, the neostriatum and the Purkinje cells of the cerebellum compared with wild-type mice

• however, mice do not exhibit ubiquitinated FTLD-FUS-like inclusions

abnormal neuromuscular synapse morphology ( J:189360 )

• mice exhibit fewer motor units in muscles compared with wild-type mice

abnormal spinal cord morphology ( J:189360 )

• ALS-like pathology

motor neuron degeneration ( J:189360 )

• in the anterior horn and white matter tracts of the spinal cord

muscle

abnormal skeletal muscle fiber type ratio ( J:189360 )

• mice exhibit a loss of glycolytic fast-twitch muscle fibers compared with wild-type mice

muscular atrophy ( J:189360 )

• at end-stage

abnormal muscle physiology ( J:189360 )

• mice exhibit increased fatigue resistance compared with wild-type mice

impaired skeletal muscle contractility ( J:189360 )

• mice exhibit weaker twitch and tetanic force compared with wild-type mice

impaired muscle relaxation ( J:189360 )

growth/size/body

slow postnatal weight gain ( J:189360 )

• from 4 weeks

hematopoietic system

microgliosis ( J:189360 )

• in the anterior horn and white matter tracts of the spinal cord

immune system

microgliosis ( J:189360 )

• in the anterior horn and white matter tracts of the spinal cord

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 6		DOID:0060198	OMIM:608030	J:189360