Phenotypes Associated with This Genotype

Genotype
MGI:5707946

• Allelic Composition: Tg(Thy1-DCTN1*G59S)M2Pcw/?
• Genetic Background: involves: C57BL/6 * SJL

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

behavior/neurological

limb grasping ( J:132857 )

• when suspended by the tail, mice fail to extend their hind limbs

tremors ( J:132857 )

• mice show spontaneous tremors that progress with age

decreased grip strength ( J:132857 )

• tremor precedes decline in grip strength in both the fore and hind limbs

abnormal gait ( J:132857 )

• gait abnormalities follow formation of tremors

paralysis ( J:132857 )

• mice eventually become paralyzed

growth/size/body

weight loss ( J:132857 )

• in the weeks leading up to end-stage of disease, mice fail to groom and lose weight

muscle

abnormal skeletal muscle fiber morphology ( J:132857 )

• the normal random distribution of muscle fiber types is replaced by fiber type grouping at end stage of disease

muscular atrophy ( J:132857 )

• electromyographic analysis shows spontaneous fibrillations characteristic of denervation indicating that mice exhibit denervation muscle atrophy

• onset of muscular atrophy signs occurs at about 5-6 months of age

progressive muscle weakness ( J:132857 )

• mice develop weakness accompanied by muscle wasting in hind limbs

nervous system

astrocytosis ( J:132857 )

• astrocytic gliosis in the spinal cord

abnormal motor neuron morphology ( J:132857 )

• cellular abnormalities in motor neurons in lumbar, thoracic and cervical spinal cord and motor neurons in the brainstem

• motor neurons of ventral spinal cord at the lumbar levels accumulate intracellular vesicles

• motor neurons show increased number of dilated endoplasmic reticulum structures and an increase in autophagosomes

decreased motor neuron number ( J:132857 )

• the number of large motor neurons in the lumbar region is reduced by about 44% at the end stage of disease

abnormal axon morphology ( J:132857 )

• swollen axons, particularly in the ventral root exit zone, that are densely packed with nonphosphorylated neurofilaments

• sensory neuropathy is seen at the end stage of disease, with mice showing reduced intraepithelial nerve fiber densities in the skin as well as degeneration within the dorsal roots

abnormal neuromuscular synapse morphology ( J:132857 )

• neuromuscular junctions show nodules, preterminal accumulations, and intrajunctional and extrajunctional sprouting

chromatolysis ( J:132857 )

• subsets of motor neurons show chromatolysis, with swollen bodies and eccentric nuclei

neuronal cytoplasmic inclusions ( J:132857 )

• motor neurons contain ubiquitin positive intracellular inclusions that are also positive for the mutant protein

• cytoplasmic inclusions in motor neurons appear as early as 2 months of age and gradually become larger

abnormal ventral spinal root morphology ( J:132857 )

• selective loss of large caliber axons in the ventral roots from the lumber region of the spinal cord

• however, abnormalities in the upper motor neurons are not seen

axon degeneration ( J:132857 )

• selective loss of large caliber axons in the ventral roots from the lumber region of the spinal cord

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:132857