Phenotypes Associated with This Genotype

Genotype
MGI:4361717

• Allelic Composition: Tg(Prnp-TARDBP*A315T)95Balo/0
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

premature death ( J:153197 )

• average survival is 154 days; at end-stage, mice die spontaneously or are euthanized when they lose righting reflex or can no longer obtain food and water

growth/size/body

weight loss ( J:153197 )

• mice begin losing weight around 4.5 months of age

behavior/neurological

abnormal gait ( J:153197 )

• at 3-4 months mice develop abnormal gait; around 4.5 months, mice exhibit a "swimming" gait when they lose ability to support their body weight but still use their limbs for propulsion to slide on their stomachs

nervous system

astrocytosis ( J:153197 )

• activation of astrocytes is detected in layer 5 with reactive astrocytosis seen around degenerating neurons

abnormal neuron morphology ( J:153197 )

• late-stage mice have cytoplasmic accumulation of ubiquinated proteins in neurons of cortical layer 5; these neurons are prominent in the motor cortex and are also present in orbital, cingulated, sensory and other cortical regions

• no ubiquinated protein aggregates are observed in the caudate/putamen, substantia nigra, thalamus or other structures at any stage

neuron degeneration ( J:153197 )

• neuron loss in cortical layer 5

motor neuron degeneration ( J:153197 )

• fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns

• femoral motor and sensory nerves shows loss of axons with ongoing axonal degeneration in the motor branch

abnormal spinal cord morphology ( J:153197 )

• fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns

decreased motor neuron number ( J:153197 )

• in end-stage mice, about a 20% loss of spinal motor neurons is observed

abnormal spinal cord ventral horn morphology ( J:153197 )

• presence of ubiquitinated protein accumulations is detected preferentially in large neurons of the dorsal horn as well as scattered interneurons

muscle

abnormal skeletal muscle morphology ( J:153197 )

• end-stage mice have scattered and grouped atrophic muscle fibers, characteristic of muscle denervation

abnormal skeletal muscle fiber morphology ( J:153197 )

• atrophic muscle fibers are observed in end-stage mice

abnormal muscle electrophysiology ( J:153197 )

• electromyography in end-stage mice shows numerous fibrillation potentials indicative of loss of muscle fiber innervation and fasciculations, which are spontaneous firing of motor units often seen with human motor neuron diseases; in presymptomatic and early-stage mice, electromyography is normal

muscle weakness ( J:153197 )

• around 4.5 months, mice can no longer support their body weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:153197
frontotemporal dementia		DOID:9255	OMIM:600274	J:153197