Phenotypes Associated with This Genotype

Genotype
MGI:7311612

• Allelic Composition: Tardbp^tm1.1Sobue/Tardbp^tm1.1Sobue; Tg(SLC18A3-cre)Misa/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * C57BL/6NTac

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:324570 )

• mice develop progressive motor dysfunction

tremors ( J:324570 )

• tremor appears as early as 50 weeks

impaired coordination ( J:324570 )

• motor performance in the rotarod task is lower beginning at 75 weeks of age

decreased grip strength ( J:324570 )

• grip strength is lower beginning at 85 weeks of age

short stride length ( J:324570 )

• average length of hindpaw steps is shorter than in controls at 100 weeks of age

cellular

abnormal autophagosome formation ( J:324570 )

• cell bodies and axons of motor neurons and sciatic nerve of 100-week-old mice show accumulation of autophagy-related structures such as autolysosomes and autophagosomes

growth/size/body

weight loss ( J:324570 )

• mice show progressive weight loss beginning around 60 weeks of age

homeostasis/metabolism

abnormal autophagosome formation ( J:324570 )

• cell bodies and axons of motor neurons and sciatic nerve of 100-week-old mice show accumulation of autophagy-related structures such as autolysosomes and autophagosomes

muscle

muscular atrophy ( J:324570 )

• muscle atrophy of the trunk and hind limb is detectable around 60 weeks of age

nervous system

astrocytosis ( J:324570 )

• the number of astrocytes progressively increases in the ventral horn indicating astrogliosis

abnormal motor neuron morphology ( J:324570 )

• lumbar ventral horn motor neurons are smaller in 100-week-old mice

• accumulation of phosphorylated neurofilament in motor neurons

• motor neurons of the trigeminal motor, facial and hypoglossal nuclei are smaller in 100-week-old mice, however those in the oculomotor and the abductor nuclei are preserved

motor neuron degeneration ( J:324570 )

• neuronal atrophy of motor neurons is seen at 100 weeks of age, with the number of large motor neurons decreased whereas the number of small motor neurons is increased, indicating atrophy of the alpha-motor neurons

abnormal neuromuscular synapse morphology ( J:324570 )

• percentage of denervated neuromuscular junctions increases progressively after 50 weeks of age

axon degeneration ( J:324570 )

• L5 ventral root exhibit axonal degeneration in a subset of large myelinated fibers from 50 weeks of age, indicating loss of large motor axons in the ventral root

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:324570