behavior/neurological phenotype

• paralysis
  • limb paralysis
  (MGI Ref ID J:59356)

mortality/aging

• premature death
  • die between 105 and 140 days of age
  (MGI Ref ID J:59356)

nervous system phenotype

• abnormal retinal rod cell outer segment morphology
  • light exposed eyes show shortening of the rod outer segments relative to the rod inner segments
  (MGI Ref ID J:59356)

• retinal photoreceptor degeneration
  • exposure to constant bright light for 20 days causes specific degeneration of photoreceptor cells
  (MGI Ref ID J:59356)

vision/eye phenotype

• thin retinal outer nuclear layer
  • light exposed eyes show a decrease in the thickness of the retinal outer nuclear layer due to loss of photoreceptor cells compared to controls
  (MGI Ref ID J:59356)

• retinal photoreceptor degeneration
  • exposure to constant bright light for 20 days causes specific degeneration of photoreceptor cells
  (MGI Ref ID J:59356)

• abnormal eye electrophysiology
  • exposure to constant bright light for 20 days causes a diminution of electroretinographic activity
  (MGI Ref ID J:59356)

• abnormal retinal rod cell outer segment morphology
  • light exposed eyes show shortening of the rod outer segments relative to the rod inner segments
  (MGI Ref ID J:59356)

growth/size/body region phenotype

• weight loss
  • mice show decrease in body weight compared to controls from 14-16 weeks after birth onwards
  (MGI Ref ID J:131028)

• decreased body weight
  • body mass and body weight is lower in symptomatic (75 days of age) and early symptomatic (105 days of age) mutants
  (MGI Ref ID J:91800)

homeostasis/metabolism phenotype

• decreased circulating insulin level
  (MGI Ref ID J:91800)

• decreased circulating leptin level
  • plasma leptin levels are diminished
  (MGI Ref ID J:91800)

• abnormal gas homeostasis
  (MGI Ref ID J:91800)

• impaired adaptive thermogenesis
  • unable to maintain body temperature when placed under conditions in which adaptive thermogenesis is challenged; show lower rectal temperature than wild-type when fasted for 24 hours or exposed to 4 degrees C
  (MGI Ref ID J:91800)

• increased oxygen consumption
  • exhibit higher rates of total oxygen consumption
  (MGI Ref ID J:91800)

• abnormal circulating hormone level
  (MGI Ref ID J:91800)

• increased circulating glucose level
  • exhibit a higher fasting glycemia than wild-type, although no differences are seen under normal feeding conditions
  (MGI Ref ID J:91800)

• decreased circulating triiodothyronine level
  • plasma T3 levels are decreased in older early symptomatic (105 days old) mutants
  (MGI Ref ID J:91800)

• increased circulating corticosterone level
  (MGI Ref ID J:91800)

• abnormal glucose homeostasis
  • fasted homozygotes clear glucose more efficiently than wild-type when injected with glucose
  (MGI Ref ID J:91800)
  • fasted mutants incorporate a nonmetabolizable glucose analog in white adipose tissue and skeletal muscle
  (MGI Ref ID J:91800)

• abnormal lipid homeostasis
  (MGI Ref ID J:91800)

• abnormal energy expenditure
  • exhibit increased energy expenditure at rest
  (MGI Ref ID J:91800)

• abnormal glycerol level
  • norepinephrine-stimulated glycerol release is higher in white adipose tissue transplants than in wild-type, indicating an increase of activated lipolysis
  (MGI Ref ID J:91800)

• decreased respiratory quotient
  • respiratory quotient is lower
  (MGI Ref ID J:91800)

• enhanced lipolysis
  (MGI Ref ID J:91800)

• increased circulating ketone body level
  • levels of circulating ketone bodies, an indicator of fatty acid oxidation, increase with age
  (MGI Ref ID J:91800)

adipose tissue phenotype

• decreased white adipose tissue amount
  • seen in both asymptomatic and symptomatic homozygotes
  (MGI Ref ID J:91800)

• abnormal adipose tissue morphology
  • exhibit reduced adipose tissue accumulation
  (MGI Ref ID J:91800)

• abnormal fat pad morphology
  • epididymal and retroperitoneal white adipose tissue is markedly reduced or almost nonexistent in the asymptomatic phase of the disease
  (MGI Ref ID J:91800)

mortality/aging

• premature death
  • compensating the energetic imbalance with a highly energetic diet extends the mean survival by 20% and improves motor neuronal function
  (MGI Ref ID J:91800)
  • none survive past 4 months of age
  (MGI Ref ID J:22628)

muscle phenotype

• abnormal muscle physiology
  • exhibit skeletal muscle hypermetabolism as indicated by increased muscle expression of genes involved in lipid and carbohydrate metabolism
  (MGI Ref ID J:91800)

• muscle degeneration
  • exhibit progressive muscle wasting
  (MGI Ref ID J:22628)

nervous system phenotype

• abnormal hypoglossal nucleus morphology
  • neuron loss is also seen in the hypoglossal nucleus but it is more variable and much milder than the loss in the facial nucleus
  (MGI Ref ID J:58733)

• abnormal spinal cord ventral horn morphology
  • exhibit moderate to severe degenerative changes within the ventral horns
  (MGI Ref ID J:22628)
  • exhibit numerous dystrophic neurites in the ventral horn gray matter, large and small argyrophilic perikarya, and swollen fragmented processes
  (MGI Ref ID J:22628)

• motor neuron degeneration
  • exhibit degeneration of a few cortical motorneurons in layer V
  (MGI Ref ID J:22628)
  • exhibit pronounced loss of large spinal motorneurons, with remaining motorneurons showing pyknosis and karyorrhexis
  (MGI Ref ID J:22628)

• neurodegeneration
  • exhibit neurodegeneration of motorneurons within the spinal cord, brain stem, and neocortex and show some degenerative changes in the hypothalamus, deep layers of the superior colliculus, deep cerebellar nuclei, basal ganglia, and thalamus
  (MGI Ref ID J:22628)

• abnormal oculomotor nucleus morphology
  • consistent neuronal loss in the oculomotor nucleus is seen only in the two most severely affected mice
  (MGI Ref ID J:58733)

• abnormal spinal cord dorsal horn morphology
  • exhibit a few dystrophic neurites in the dorsal horn, however do not detect any argyrophilic perikarya
  (MGI Ref ID J:22628)

• abnormal facial motor nucleus morphology
  • exhibit a variable (16-72%) decrease in neuron number in the facial nucleus and a smaller nuclear volume
  (MGI Ref ID J:58733)

• abnormal cranial nerve morphology
  • within the brain stem and neocortex, show degenerative changes in the motor components of cranial nerve nuclei
  (MGI Ref ID J:22628)

• abnormal trigeminal motor nucleus morphology
  • exhibit a moderate deletion of neurons in the trigeminal motor nucleus
  (MGI Ref ID J:58733)

behavior/neurological phenotype

• impaired coordination
  • mice show reduced ability with aging to remain on rotating rod
  (MGI Ref ID J:131028)

• paralysis
  • develop a spastic paralysis, initially involving the hindlimbs but progressing to the forelimb, that is associated with profound muscle wasting
  (MGI Ref ID J:22628)

• decreased grip strength
  • progressive decrease in grip strength is observed starting at around 15 weeks of age
  (MGI Ref ID J:131028)

• weakness
  • at 3-4 months of age, develop a generalized weakness that progresses within 72 hours to total immobility
  (MGI Ref ID J:22628)

• impaired balance
  • animals show increased incidence of falling
  (MGI Ref ID J:131028)

• aphagia
  • cease food and water intake
  (MGI Ref ID J:22628)

• abnormal motor capabilities/coordination/movement
  • exhibit an age-related rapidly progressive decline of motor function
  (MGI Ref ID J:22628)