Phenotypes Associated with This Genotype

Genotype
MGI:5618534

• Allelic Composition: Tg(Prnp-FUS*R521C)3313Ejh/0
• Genetic Background: involves: C57BL/6 * SJL

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

mortality/aging

premature death ( J:209419 )

• most mice die within 4-6 weeks of the onset of symptoms

behavior/neurological

abnormal motor learning ( J:209419 )

• poor performance and motor learning on rotarod test

limb grasping ( J:209419 )

• most mice exhibit prolonged hind limb clasping (100 seconds vs 10 seconds) during the tail suspension test

abnormal motor coordination/balance ( J:209419 )

• motor coordination defects

abnormal gait ( J:209419 )

hindlimb paralysis ( J:209419 )

• most mice exhibit severe spastic paraplegia

• mice have a reduced distance between hind paws during tandem walk tests

spasticity ( J:209419 )

• most mice exhibit severe spastic paraplegia

cellular

abnormal cell physiology ( J:209419 )

• DNA damage is observed in cortical and spinal motor neurons

• 50% of neurons exhibit comet tails as compared to 20% in controls

• genes involved in dendritic growth and synaptic function exhibit defects in transcription and RNA processing

growth/size/body

postnatal growth retardation ( J:209419 )

• most mice exhibit growth retardation

muscle

muscle degeneration ( J:209419 )

• most mice exhibit severe muscle wasting

nervous system

decreased motor neuron number ( J:209419 )

abnormal dendrite morphology ( J:209419 )

• primitive dendritic branching is observed in motor neurons of 2-3 month old mice

• cumulative dendritic area is reduced as early as P18

• number of dendritic branches and cumulative dendritic area are reduced in pyramidal neurons of the sensorimotor cortex

abnormal dendritic spine morphology ( J:209419 )

• total spine and mature spine densities are reduced on the apical and secondary dendrites of neurons in the sensorimotor cortex

abnormal neuromuscular synapse morphology ( J:209419 )

• majority of neuromuscular junctions in diaphragm exhibit partial or complete loss of innervation by 1-3 months of age

• postsynaptic density and number of synapses per unit area is reduced in spinal motor neurons and sensorimotor cortex

neurodegeneration ( J:209419 )

motor neuron degeneration ( J:209419 )

• mice exhibit 55% loss of choline acetyltransferase positive (ChAT+) spinal motor neurons by end of life (1-3 months)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 6		DOID:0060198	OMIM:608030	J:209419