Phenotypes Associated with This Genotype

Genotype
MGI:6883565

• Allelic Composition: Setx^tm1.1Als/Setx⁺
• Genetic Background: involves: 129 * 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

• ventral horn motor neurons show nuclear membrane defects

motor neuron degeneration ( J:320844 )

• degeneration of ventral horn motor neurons

• mice show a decrease in the number of spinal cord motor large caliber axons in the L5 root

• however, no significant difference in the numbers of choline acetyltransferase-positive neurons is seen in lumbar spinal cord, although a modest, non-significant, reduction is seen

abnormal neuromuscular synapse morphology ( J:320844 )

• mice show similar numbers of innervated skeletal muscle contacts, although they show a modest increase in the number of innervated neuromuscular junctions

abnormal neuron physiology ( J:320844 )

• primary cortical neurons show impaired nucleocytoplasmic transport

increased susceptibility to neuronal excitotoxicity ( J:320844 )

• primary cortical neurons show a nearly 2-fold increase in cell death upon propidium iodide exclusion assay

• cultured cerebellar granule neurons show increased susceptibility to cell death upon potassium chloride withdrawal

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:320844 )

• primary cortical neurons show a nearly 2-fold increase in cell death upon propidium iodide exclusion assay

• cultured cerebellar granule neurons show increased susceptibility to cell death upon potassium chloride withdrawal

cellular

increased susceptibility to neuronal excitotoxicity ( J:320844 )

• primary cortical neurons show a nearly 2-fold increase in cell death upon propidium iodide exclusion assay

• cultured cerebellar granule neurons show increased susceptibility to cell death upon potassium chloride withdrawal

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