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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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Prnp-PFN1*C71G)22Zxu mutation (1 available)
Tg(Thy1-PFN1*C71G)67Zxu mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• reduced grip strength beginning at 121-150 days
• impaired vertical behavior beginning at 121-150 days
• paralysis at 211 +/-25 days

cellular
• 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
• reduced body weight beginning at 121-150 days

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

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

mortality/aging
• due to paralysis

muscle
• clusters of oxidative (SDH-strong) and weak oxidative (SDH-weak) fibers as compared to interspersed distribution found in control
• 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 is increased in ventral horn of spinal cord at the end stage of disease
• astrogliosis is increased in ventral horn of spinal cord at the end stage of disease
• motor neurons have reduced neurofilaments, lack a well-spread filament network and exhibit a circular distribution of neurofilaments around the cell periphery
• increased muscle denervation
• 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
• 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
• increased cellulation (and GFAP staining) in medulla
• neuronal loss is not observed in cerebral cortex, hippocampus or cerebellum
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
01/09/2018
MGI 6.11
The Jackson Laboratory