Phenotypes Associated with This Genotype

Genotype
MGI:3687994

• Allelic Composition: Tg(Sod1*G86R)M1Jwg/0
• Genetic Background: involves: FVB/N

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

mortality/aging

premature death ( J:22628 , J:91800 )

• none survive past 4 months of age (J:22628)

• compensating the energetic imbalance with a highly energetic diet extends the mean survival by 20% and improves motor neuronal function (J:91800)

behavior/neurological

aphagia ( J:22628 )

• cease food and water intake

abnormal motor capabilities/coordination/movement ( J:22628 )

• exhibit an age-related rapidly progressive decline of motor function

impaired balance ( J:131028 )

• animals show increased incidence of falling

impaired coordination ( J:131028 )

• mice show reduced ability with aging to remain on rotating rod

decreased grip strength ( J:131028 )

• progressive decrease in grip strength is observed starting at around 15 weeks of age

weakness ( J:22628 )

• at 3-4 months of age, develop a generalized weakness that progresses within 72 hours to total immobility

paralysis ( J:22628 )

• develop a spastic paralysis, initially involving the hindlimbs but progressing to the forelimb, that is associated with profound muscle wasting

nervous system

abnormal hypoglossal nucleus morphology ( J:58733 )

• neuron loss is also seen in the hypoglossal nucleus but it is more variable and much milder than the loss in the facial nucleus

abnormal oculomotor nucleus morphology ( J:58733 )

• consistent neuronal loss in the oculomotor nucleus is seen only in the two most severely affected mice

abnormal facial motor nucleus morphology ( J:58733 )

• exhibit a variable (16-72%) decrease in neuron number in the facial nucleus and a smaller nuclear volume

abnormal trigeminal motor nucleus morphology ( J:58733 )

• exhibit a moderate deletion of neurons in the trigeminal motor nucleus

abnormal cranial nerve morphology ( J:22628 )

• within the brain stem and neocortex, show degenerative changes in the motor components of cranial nerve nuclei

abnormal spinal cord dorsal horn morphology ( J:22628 )

• exhibit a few dystrophic neurites in the dorsal horn, however do not detect any argyrophilic perikarya

abnormal spinal cord ventral horn morphology ( J:22628 )

• exhibit moderate to severe degenerative changes within the ventral horns

• exhibit numerous dystrophic neurites in the ventral horn gray matter, large and small argyrophilic perikarya, and swollen fragmented processes

neurodegeneration ( J:22628 )

• 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

motor neuron degeneration ( J:22628 )

• exhibit pronounced loss of large spinal motorneurons, with remaining motorneurons showing pyknosis and karyorrhexis

• exhibit degeneration of a few cortical motorneurons in layer V

muscle

muscle degeneration ( J:22628 )

• exhibit progressive muscle wasting

abnormal muscle physiology ( J:91800 )

• exhibit skeletal muscle hypermetabolism as indicated by increased muscle expression of genes involved in lipid and carbohydrate metabolism

adipose tissue

abnormal adipose tissue morphology ( J:91800 )

• exhibit reduced adipose tissue accumulation

decreased white adipose tissue amount ( J:91800 )

• seen in both asymptomatic and symptomatic homozygotes

abnormal fat pad morphology ( J:91800 )

• epididymal and retroperitoneal white adipose tissue is markedly reduced or almost nonexistent in the asymptomatic phase of the disease

growth/size/body

decreased body weight ( J:91800 )

• body mass and body weight is lower in symptomatic (75 days of age) and early symptomatic (105 days of age) mutants

weight loss ( J:131028 )

• mice show decrease in body weight compared to controls from 14-16 weeks after birth onwards

homeostasis/metabolism

impaired adaptive thermogenesis ( J:91800 )

• 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

abnormal circulating hormone level ( J:91800 )

decreased circulating triiodothyronine level ( J:91800 )

• plasma T3 levels are decreased in older early symptomatic (105 days old) mutants

decreased circulating insulin level ( J:91800 )

decreased circulating leptin level ( J:91800 )

• plasma leptin levels are diminished

abnormal energy expenditure ( J:91800 )

• exhibit increased energy expenditure at rest

abnormal gas homeostasis ( J:91800 )

increased oxygen consumption ( J:91800 )

• exhibit higher rates of total oxygen consumption

decreased respiratory quotient ( J:91800 )

• respiratory quotient is lower

abnormal glucose homeostasis ( J:91800 )

• fasted homozygotes clear glucose more efficiently than wild-type when injected with glucose

• fasted mutants incorporate a nonmetabolizable glucose analog in white adipose tissue and skeletal muscle

increased circulating glucose level ( J:91800 )

• exhibit a higher fasting glycemia than wild-type, although no differences are seen under normal feeding conditions

abnormal lipid homeostasis ( J:91800 )

increased circulating corticosterone level ( J:91800 )

increased circulating ketone body level ( J:91800 )

• levels of circulating ketone bodies, an indicator of fatty acid oxidation, increase with age

abnormal glycerol level ( J:91800 )

• norepinephrine-stimulated glycerol release is higher in white adipose tissue transplants than in wild-type, indicating an increase of activated lipolysis

enhanced lipolysis ( J:91800 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:22628 , J:58733 , J:91800