Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-SOD1*G93A)T3Hgrd
• Allele Name: transgene insertion T3, Casper Hoogenraad
• Allele ID: MGI:3785090
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Thy1-SOD1*G93A)T1Hgrd/0 Tg(Thy1-SOD1*G93A)T3Hgrd/0	involves: C57BL/6 * CBA * FVB	MGI:3785389
cx2	Tg(SOD1*G93A)^dl1Gur/0 Tg(Thy1-SOD1*G93A)T3Hgrd/0	involves: C57BL/6 * CBA * FVB * SJL	MGI:3785391
cx3	Tg(SOD1)2Gur/0 Tg(Thy1-SOD1*G93A)T3Hgrd/0	involves: C57BL/6 * CBA * FVB * SJL	MGI:3785393
tg4	Tg(Thy1-SOD1*G93A)T3Hgrd/Tg(Thy1-SOD1*G93A)T3Hgrd	involves: C57BL/6 * CBA * FVB	MGI:3785390
tg5	Tg(Thy1-SOD1*G93A)T3Hgrd/0	involves: C57BL/6 * CBA * FVB	MGI:3785387

Genotype
MGI:3785389

cx1

• Allelic Composition: Tg(Thy1-SOD1*G93A)T1Hgrd/0; Tg(Thy1-SOD1*G93A)T3Hgrd/0
• Genetic Background: involves: C57BL/6 * CBA * FVB

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

growth/size/body

weight loss ( J:134095 )

• at end-stage, most mice display severe weight loss (>30%)

behavior/neurological

abnormal motor coordination/balance ( J:134095 )

• at end-stage, severe locomotor deficits are exhibited

impaired coordination ( J:134095 )

• at end-stage, loss of ability to hang in hanging wire test

abnormal grip strength ( J:134095 )

• loss of grip strength at end-stage of disease

nervous system

abnormal brain morphology ( J:134095 )

• accumulation of argyrophilic neuronal debris is seen throughout medullary, pontine, and mesencephalic reticular formation up to zona incerta

gliosis ( J:134095 )

• signs of reactive gliosis are seen at disease end-stage

abnormal neurite morphology ( J:134095 )

• animals not displaying motor abnormalities show ubiquinated neurites in spinal cord

abnormal neuromuscular synapse morphology ( J:134095 )

• in mice at end-stage, denervation is observed at neuromuscular synapses

neuron degeneration ( J:134095 )

• appears restricted to brainstem and spinal cord

abnormal spinal cord morphology ( J:134095 )

• accumulation of argyrophilic neuronal debris is seen in spinal cord of mice at end-stage of disease; similar amounts are seen between left and right, and lumbar and cervical segments

decreased motor neuron number ( J:134095 )

• loss of motor neurons is detected at disease end-stage

muscle

progressive muscle weakness ( J:134095 )

• exhibited by most mice (67%) before 2 years of age; onset is observed at 539 days to more than 730 days with end stage reached at 591 to greater than 730 days

cellular

cellular phenotype ( J:134095 )

N • mice do not develop mitochondrial swelling and vacuolization like G1 or G1del mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:134095

Genotype
MGI:3785391

cx2

• Allelic Composition: Tg(SOD1*G93A)^dl1Gur/0; Tg(Thy1-SOD1*G93A)T3Hgrd/0
• Genetic Background: involves: C57BL/6 * CBA * FVB * SJL

behavior/neurological

impaired coordination ( J:134095 )

• inability to perform hanging wire test

muscle

muscle weakness ( J:134095 )

• first sign of disease is forelimb weakness

progressive muscle weakness ( J:134095 )

• the T3 transgene has marginal effects on disease onset and survival in the G1del mutants; onset is 168 to 197 days with end-stage reached at 210-248 days

• animals show forelimb onset of disease

Genotype
MGI:3785393

cx3

• Allelic Composition: Tg(SOD1)2Gur/0; Tg(Thy1-SOD1*G93A)T3Hgrd/0
• Genetic Background: involves: C57BL/6 * CBA * FVB * SJL

nervous system

abnormal oligodendrocyte morphology ( J:134095 )

• ubiquinated SOD1 aggregates are seen at >45 weeks

abnormal innervation pattern to muscle ( J:134095 )

• muscle denervation is seen at end-stage of disease (<80 weeks)

decreased motor neuron number ( J:134095 )

• motor neuron loss characterizes end-stage of disease (<80 weeks)

abnormal dendrite morphology ( J:134095 )

• ubiquinated dendritic SOD1 aggregates develop; these are present as early as 15-20 weeks

behavior/neurological

paralysis ( J:134095 )

• most mice show total paralysis of at least one hind limb; at end-stage, >80% of mice display fully immobilized hindlimbs

muscle

muscle weakness ( J:134095 )

• develops at about 1 year of age

• reach end-stage of disease before 80 weeks

• 60% of animals show hindlimb onset of disease while subset displays forelimb onset with short disease duration

Genotype
MGI:3785390

tg4

• Allelic Composition: Tg(Thy1-SOD1*G93A)T3Hgrd/Tg(Thy1-SOD1*G93A)T3Hgrd
• Genetic Background: involves: C57BL/6 * CBA * FVB

growth/size/body

weight loss ( J:134095 )

• at end-stage, most mice display severe weight loss (>30%)

nervous system

abnormal brain morphology ( J:134095 )

• accumulation of argyrophilic neuronal debris is seen throughout medullary, pontine, and mesencephalic reticular formation up to zona incerta

astrocytosis ( J:134095 )

• signs of reactive gliosis are seen at disease end-stage

abnormal neurite morphology ( J:134095 )

• animals not displaying motor abnormalities show ubiquinated neurites in spinal cord

abnormal neuromuscular synapse morphology ( J:134095 )

• in mice at end-stage, denervation is observed at neuromuscular synapses

neuron degeneration ( J:134095 )

• appears restricted to brainstem and spinal cord

abnormal spinal cord morphology ( J:134095 )

• accumulation of argyrophilic neuronal debris is seen in spinal cord of mice at end-stage of disease; similar amounts are seen between left and right, and lumbar and cervical segments

decreased motor neuron number ( J:134095 )

• loss of motor neurons is detected at disease end-stage

behavior/neurological

abnormal motor coordination/balance ( J:134095 )

• at end-stage, severe locomotor deficits are exhibited

impaired coordination ( J:134095 )

• at end-stage, loss of ability to hang in hanging wire test

abnormal grip strength ( J:134095 )

• loss of grip strength at end-stage of disease

muscle

progressive muscle weakness ( J:134095 )

• exhibited by most mice (60%) before 2 years of age; onset is observed at 378 to >730 days with end stage reached at >432 to >730 days

cellular

cellular phenotype ( J:134095 )

N • mice do not develop mitochondrial swelling and vacuolization like G1 or G1del mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:134095

Genotype
MGI:3785387

tg5

• Allelic Composition: Tg(Thy1-SOD1*G93A)T3Hgrd/0
• Genetic Background: involves: C57BL/6 * CBA * FVB

behavior/neurological

behavior/neurological phenotype ( J:134095 )

N • mice show no clinical or pathological signs of motor abnormalities up to 2 years of age