Phenotypes Associated with This Genotype

Genotype
MGI:6883568

• Allelic Composition: Tg(Prnp-SETX*R2136H)1920Als/0
• Genetic Background: involves: C57BL/6J

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:320844 )

• mice show onset of motor abnormalities at 6 months of age

limb grasping ( J:320844 )

• mice show increased hindlimb clasping starting at 6 months of age

impaired coordination ( J:320844 )

• mice show a progressive increase in dysfunction on the ledge test starting at 6 months of age

• mice show impaired motor coordination on the rotarod beginning at 6 months of age and progressively worsens with age

nervous system

abnormal motor neuron morphology ( J:320844 )

• mice show mislocalization of TDP-43 in lumbar spinal cord; mislocalization is prominent in motor neurons and is also present in glia

• approximately 10% of ventral horn motor neurons show TDP-43 mislocalization

• however, TDP-43 mislocalization in the cortex is not seen

motor neuron degeneration ( J:320844 )

• degeneration of ventral horn motor neurons

• however, no difference in the numbers of choline acetyltransferase-positive neurons is seen in lumbar spinal cord

abnormal neuron physiology ( J:320844 )

• primary spinal cord motor neurons from E13 embryos grown in culture and exposed to sodium arsenite, an inducer of oxidative stress, show an increase in stress granule formation compared to wild-type motor neurons

increased susceptibility to neuronal excitotoxicity ( J:320844 )

• primary spinal cord motor neurons from E13 embryos grown in culture and treated with staurosporine show an increase in apoptotic activation compared to wild-type motor neurons

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:320844 )

• primary spinal cord motor neurons from E13 embryos grown in culture and treated with staurosporine show an increase in apoptotic activation compared to wild-type motor neurons

cellular

increased susceptibility to neuronal excitotoxicity ( J:320844 )

• primary spinal cord motor neurons from E13 embryos grown in culture and treated with staurosporine show an increase in apoptotic activation compared to wild-type motor neurons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 4		DOID:0060196	OMIM:602433	J:320844