Phenotypes Associated with This Genotype

Genotype
MGI:5800513

• Allelic Composition: Tg(Prnp-PFN1*C71G)22Zxu/0; Tg(Thy1-PFN1*C71G)67Zxu/Tg(Thy1-PFN1*C71G)67Zxu
• Genetic Background: involves: FVB/N

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

behavior/neurological

decreased grip strength ( J:235427 )

• reduced grip strength beginning at 121-150 days

decreased vertical activity ( J:235427 )

• impaired vertical behavior beginning at 121-150 days

paralysis ( J:235427 )

• paralysis at 211 +/-25 days

cellular

abnormal cell cytoskeleton morphology ( J:235427 )

• motor neurons have reduced neurofilaments, lack a well-spread filament network and exhibit a circular distribution of neurofilaments around the cell periphery

growth/size/body

decreased body weight ( J:235427 )

• reduced body weight beginning at 121-150 days

hematopoietic system

microgliosis ( J:235427 )

• microgliosis is increased in ventral horn of spinal cord at the end stage of disease

immune system

microgliosis ( J:235427 )

• microgliosis is increased in ventral horn of spinal cord at the end stage of disease

mortality/aging

premature death ( J:235427 )

• due to paralysis

muscle

skeletal muscle fiber atrophy ( J:235427 )

increased variability of skeletal muscle fiber size ( J:235427 )

• clusters of oxidative (SDH-strong) and weak oxidative (SDH-weak) fibers as compared to interspersed distribution found in control

progressive muscle weakness ( J:235427 )

• 10% of mice between 100-120 days old exhibit slight weakness (foot dragging)

• 70% of mice between 121-140 days old exhibit slight weakness

• 100% of mice between 141-170 days exhibit slight weakness, progressing to weakness (leg dragging)

• beyond 170 days, all mice progress from partial paralysis to paralysis in both fore and hind limbs

• impaired rotorod performance beginning at 121-150 days

nervous system

microgliosis ( J:235427 )

• microgliosis is increased in ventral horn of spinal cord at the end stage of disease

astrocytosis ( J:235427 )

• astrogliosis is increased in ventral horn of spinal cord at the end stage of disease

abnormal motor neuron morphology ( J:235427 )

• motor neurons have reduced neurofilaments, lack a well-spread filament network and exhibit a circular distribution of neurofilaments around the cell periphery

abnormal motor neuron innervation pattern ( J:235427 )

• increased muscle denervation

decreased motor neuron number ( J:235427 )

• motor neuron number is reduced in lumbar spinal cord at the end stage of disease (170-226 days)

• motor neuron number is reduced in the ventral horn of cervical spinal cord beginning at 132-154 days of age

neuronal cytoplasmic inclusions ( J:235427 )

• protein aggregates are visible by day 127 and gradually accumulate until death

• motor neurons exhibit widespread small particulates in the cytoplasm and neuronal processe

• 1-2% of motor neurons form large aggregates

• strong ubiquitin staining is present in motor neurons and some neuropils

• p62/SQSTM1 staining is present as small particulates in cytoplasm of motor neurons

neurodegeneration ( J:235427 )

• increased cellulation (and GFAP staining) in medulla

• neuronal loss is not observed in cerebral cortex, hippocampus or cerebellum

motor neuron degeneration ( J:235427 )

axon degeneration ( J:235427 )

• axon loss is progressive

• increased number of degenerating axons in the ventral root in 100-120 day old mice as compared to controls

• axon degeneration is observed in the dorsal root, but progression lags behind ventral root axons

• axon degeneration is observed in white matter of spinal cord; degeneration is mild in lateral column and more severe in ventral column

• little axon degeneration is observed in the cortical spinal track in the dorsal column

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 18		DOID:0060209	OMIM:614808	J:235427