Phenotypes Associated with This Genotype

Genotype
MGI:8162216

• Allelic Composition: Pcdha9^em1Zhxu/Pcdha9^em1Zhxu
• Genetic Background: C57BL/6-Pcdha9^em1Zhxu

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

mortality/aging

premature death ( J:360856 )

• a few mice start to die around 5 months of age with lethality progressing with age

• some severely paralyzed mice die within 2 weeks of the onset of paralysis

growth/size/body

weight loss ( J:360856 )

• body weight starts to decline after reaching a peak around 7 months of age and the decline becomes significant at 12 months

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:360856 )

• mice exhibit progressive motor dysfunction

• mice show frequent abnormal claw movement and hindlimb overextension when hung by their tail

impaired coordination ( J:360856 )

• mice show deficits on the rotarod at 12 months of age

impaired limb coordination ( J:360856 )

• mice show defects in limb coordination during the swimming test at 12 months of age

decreased grip strength ( J:360856 )

• both forearm and four-limb grip strength becomes weaker at 12 months of age, but is not significant at 10 months or younger

abnormal gait ( J:360856 )

• mice have severely abnormal gaits at 12 months of age

short stride length ( J:360856 )

• stride length of the stance of the hind limbs is slightly shorter as early as 4 months, becomes obviously shorter at 8 months and gets more severe with age

hemiplegia ( J:360856 )

• most mice are paralyzed at 14 months; paralysis usually starts unilaterally, affecting limbs on one side at a time

• some severely paralyzed mice die within 2 weeks of the onset of paralysis

muscle

muscular atrophy ( J:360856 )

• severe muscle wasting, with size and weight of the gastrocnemius muscle reduced at 13 months

• atrophied muscle cells with centrally localized nuclei are more obvious at 14 months than at 12 months

• atrophied muscle fibers indicate that muscle atrophy is neurogenic

abnormal muscle electrophysiology ( J:360856 )

• electromyography detects abundant positive sharp waves, fibrillations, and spontaneous and giant motor unit potential in muscles (including shoulder-deltoid muscle, trapezius dorsi muscle, and rectus femoris muscle) corresponding to multiple spinal cord segments at 13 months of age which are not seen in wild-type mice; the spontaneous potentials are not symmetric between the two sides of each muscle

nervous system

astrocytosis ( J:360856 )

• reactive astrocytosis in the vicinity of motor neurons

motor neuron degeneration ( J:360856 )

• a significant loss of CHAT+ motor neurons in the ventral horn of the lumbar spinal cord (L3-L5) region is seen at 12, but not 10, months of age

• reduction of total neurons (NeuN+) in the ventral horn

abnormal synaptic bouton morphology ( J:360856 )

• skeletal neuromuscular junctions in the semitendinosus muscles at 13 months of age show more presynaptic sites that are faint/weaker or even denervated

abnormal neuromuscular synapse morphology ( J:360856 )

• individual skeletal neuromuscular junction area is reduced in the semitendinosus muscles at 13 months of age

neuronal cytoplasmic inclusions ( J:360856 )

• in the ventral spinal cord, TDP-43 is barely detectable in the motor neuron nuclei, whereas TDP-43 is abundantly accumulated in the cytoplasm at 12 months of age, a neuropathological hallmark of sporadic amyotrophic lateral sclerosis

abnormal sciatic nerve morphology ( J:360856 )

• sciatic nerve at 13 months of age shows an increase in thinner axons and a decrease in large-diameter axons, indicating a degeneration and/or regeneration of axons and fewer large caliber alpha-axons

• however, no defect in the myelination of fibers in the spinal cord is seen at 13 months of age

skeleton

kyphosis ( J:360856 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sporadic amyotrophic lateral sclerosis		DOID:0080917		J:360856