All Phenotypes Tg(SOD1*G93A)1Gur MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1(GRN)Pvd/Gt(ROSA)26Sor^tm1(GRN)Pvd Tg(Pgk1-cre)1Lni/0 Tg(SOD1*G93A)1Gur/0	B6J.Cg-Tg(Pgk1-cre)1Lni Gt(ROSA)26Sor^tm1(GRN)Pvd Tg(SOD1*G93A)1Gur	MGI:5637746
cn2	Gt(ROSA)26Sor^tm1(GRN)Pvd/Gt(ROSA)26Sor⁺ Tg(Pgk1-cre)1Lni/0 Tg(SOD1*G93A)1Gur/0	B6J.Cg-Tg(Pgk1-cre)1Lni Gt(ROSA)26Sor^tm1(GRN)Pvd Tg(SOD1*G93A)1Gur	MGI:5637745
cx3	Gria2^tm1Rod/Gria2^tm1Rod Tg(SOD1*G93A)1Gur/0	B6.Cg-Gria2^tm1Rod Tg(SOD1*G93A)1Gur	MGI:4834606
cx4	Gria2^tm1Rod/Gria2⁺ Tg(SOD1*G93A)1Gur/0	B6.Cg-Gria2^tm1Rod Tg(SOD1*G93A)1Gur	MGI:4834607
cx5	Tcrb^tm1Mom/Tcrb⁺ Tg(SOD1*G93A)1Gur/0	B6.Cg-Tcrb^tm1Mom Tg(SOD1*G93A)1Gur/J	MGI:4822435
cx6	Sirt2^tm1.2Auw/Sirt2^tm1.2Auw Tg(SOD1*G93A)1Gur/0	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:5499286
cx7	Hdac6^tm1.1Pmt/Y Tg(SOD1*G93A)1Gur/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL	MGI:5499285
cx8	Slc1a2^tm1Kta/Slc1a2⁺ Tg(SOD1*G93A)1Gur/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL/J	MGI:4838970
cx9	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Tg(SOD1*G93A)1Gur/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4833986
cx10	Cnr1^tm1Map/Cnr1^tm1Map Tg(SOD1*G93A)1Gur/0	involves: 129S1/Sv * 129X1/SvJ * ABH * C57BL/6 * SJL	MGI:4881738
cx11	Tg(SOD1*G93A)1Gur/0 Vegfa^tm2Pec/Vegfa^tm2Pec	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:4831157
cx12	Spi1^tm1Ram/Spi1^tm1Ram Tg(SOD1*G93A)1Gur/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:3793622
cx13	Fgfbp1^tm1Gvdz/Fgfbp1^tm1Gvdz Tg(SOD1*G93A)1Gur/0 Tg(Thy1-YFP)16Jrs/0	involves: 129S5/SvEvBrd * C57BL/6J * CBA * SJL	MGI:5902841
cx14	Mmp9^tm1Tvu/Mmp9^tm1Tvu Tg(SOD1*G93A)1Gur/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1 * SJL	MGI:4367704
cx15	Tg(SOD1*G93A)1Gur/0 Tg(THY1-SNCA)1Sud/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:3768131
cx16	Als2^tm1Deng/Als2^tm1Deng Tg(SOD1*G93A)1Gur/?	involves: 129/Sv * C57BL/6 * SJL	MGI:3770665
cx17	Faah^tm1Crv/Faah^tm1Crv Tg(SOD1*G93A)1Gur/0	involves: 129X1/SvJ * ABH * C57BL/6 * SJL	MGI:4881741
cx18	Dctn1^tm1Cai/Dctn1⁺ Tg(SOD1*G93A)1Gur/0	involves: 129X1/SvJ * C57BL/6 * FVB/N * SJL	MGI:3769517
cx19	Bax^tm1Sjk/Bax^tm1Sjk Tg(SOD1*G93A)1Gur/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:4835659
cx20	Dync1h1^Cra1/Dync1h1⁺ Tg(SOD1*G93A)1Gur/?	involves: C3HeB/FeJ * C57BL/6 * SJL	MGI:3721969
cx21	Tardbp^m1H/Tardbp⁺ Tg(SOD1*G93A)1Gur/0	involves: C3H/HeH * C57BL/6 * C57BL/6J * SJL	MGI:5575774
cx22	Sod2^tm1Cje/Sod2⁺ Tg(SOD1*G93A)1Gur/0	involves: C57BL/6 * CD-1 * SJL	MGI:4831000
cx23	Tg(Myl1-Igf1)1Nros/0 Tg(SOD1*G93A)1Gur/0	involves: C57BL/6 * FVB/N * SJL	MGI:4838155
cx24	Tg(Gria2586N)238.2Rsp/0 Tg(SOD1G93A)1Gur/0	involves: C57BL/6Ico	MGI:4834300
cx25	Tg(SOD1*G93A)1Gur/0 Wld^s/Wld^s	involves: C57BL/6J * C57BL/6Ola * SJL/J	MGI:4835779
cx26	Tg(SOD1*G93A)1Gur/0 Wld^s/+	involves: C57BL/6J * C57BL/6Ola * SJL/J	MGI:4835781
cx27	Bbc3^tm1Ast/Bbc3^tm1Ast Tg(SOD1*G93A)1Gur/0	involves: C57BL/6 * NZB * SJL	MGI:3815033
cx28	Tg(SOD1)2Gur/0 Tg(SOD1*G93A)1Gur/0	involves: C57BL/6 * SJL	MGI:5449898
tg29	Tg(SOD1*G93A)1Gur/0	B6.Cg-Tg(SOD1*G93A)1Gur	MGI:4839171
tg30	Tg(SOD1*G93A)1Gur/0	B6.Cg-Tg(SOD1*G93A)1Gur/J	MGI:3693880
tg31	Tg(SOD1*G93A)1Gur/0	B6SJL-Tg(SOD1*G93A)1Gur	MGI:4829786
tg32	Tg(SOD1*G93A)1Gur/0	B6SJL-Tg(SOD1*G93A)1Gur/J	MGI:4822033
tg33	Tg(SOD1*G93A)1Gur/0	involves: ABH * C57BL/6 * SJL	MGI:4881742
tg34	Tg(SOD1*G93A)1Gur/0	involves: C57BL/6 * CD-1 * SJL	MGI:4830999
tg35	Tg(SOD1*G93A)1Gur/0	involves: C57BL/6Ico	MGI:4834309
tg36	Tg(SOD1*G93A)1Gur/0	involves: C57BL/6J * C57BL/Ola * SJL/J	MGI:4835776
tg37	Tg(SOD1*G93A)1Gur/0	involves: C57BL/6 * SJL	MGI:3688004
tg38	Tg(SOD1*G93A)1Gur/?	involves: C57BL/6 * SJL	MGI:3721970

Allelic Composition	Gt(ROSA)26Sor^tm1(GRN)Pvd/Gt(ROSA)26Sor^tm1(GRN)Pvd Tg(Pgk1-cre)1Lni/0 Tg(SOD1*G93A)1Gur/0
Genetic Background	B6J.Cg-Tg(Pgk1-cre)1Lni Gt(ROSA)26Sor^tm1(GRN)Pvd Tg(SOD1*G93A)1Gur

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Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sor^tm1(GRN)Pvd mutation (0 available); any Gt(ROSA)26Sor mutation (942 available)
Tg(Pgk1-cre)1Lni mutation (1 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:211734 )

• average lifespan is 168.4 days

nervous system

motor neuron degeneration ( J:211734 )

• onset or progression of motor neuron degeneration is similar to that seen in mice expressing only Tg(SOD1*G93A)1Gur, with an average onset of disease at 138.2 days

behavior/neurological

impaired coordination ( J:211734 )

• mice show impaired performance on the rotarod and in hanging from a grid to a similar extent as seen in mice expressing only Tg(SOD1*G93A)1Gur

Allelic Composition	Gt(ROSA)26Sor^tm1(GRN)Pvd/Gt(ROSA)26Sor⁺ Tg(Pgk1-cre)1Lni/0 Tg(SOD1*G93A)1Gur/0
Genetic Background	B6J.Cg-Tg(Pgk1-cre)1Lni Gt(ROSA)26Sor^tm1(GRN)Pvd Tg(SOD1*G93A)1Gur

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

mortality/aging

premature death ( J:211734 )

• average lifespan is 163.3 days

nervous system

motor neuron degeneration ( J:211734 )

• onset or progression of motor neuron degeneration is similar to that seen in mice expressing only Tg(SOD1*G93A)1Gur, with an average onset of disease at 134.2 days

behavior/neurological

impaired coordination ( J:211734 )

• mice show impaired performance on the rotarod and in hanging from a grid to a similar extent as seen in mice expressing only Tg(SOD1*G93A)1Gur

Allelic Composition	Gria2^tm1Rod/Gria2^tm1Rod Tg(SOD1*G93A)1Gur/0
Genetic Background	B6.Cg-Gria2^tm1Rod Tg(SOD1*G93A)1Gur

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Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gria2^tm1Rod mutation (2 available); any Gria2 mutation (75 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:104951 )

• shortened lifespan (116.50.6 vs. 137.12.6 days), compare with Tg(SOD1*G93A)1Gur mice

behavior/neurological

impaired coordination ( J:104951 )

• unable to walk on a rotarod

decreased grip strength ( J:104951 )

• decreased grip strength in forelimbs

hindlimb paralysis ( J:104951 )

• earlier onset (99.32.1 days vs. 117.31.8 days), compare with Tg(SOD1*G93A)1Gur mice

nervous system

decreased motor neuron number ( J:104951 )

• decreased number of the large neurons in the ventral horn of the lumbar spinal cord

abnormal AMPA-mediated synaptic currents ( J:104951 )

• higher elevations of the intracellular Ca2+ concentration upon AMPA receptor stimulation

Allelic Composition	Gria2^tm1Rod/Gria2⁺ Tg(SOD1*G93A)1Gur/0
Genetic Background	B6.Cg-Gria2^tm1Rod Tg(SOD1*G93A)1Gur

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gria2^tm1Rod mutation (2 available); any Gria2 mutation (75 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

nervous system

decreased motor neuron number ( J:104951 )

• decreased number of the large neurons in the ventral horn of the lumbar spinal cord

Allelic Composition	Tcrb^tm1Mom/Tcrb⁺ Tg(SOD1*G93A)1Gur/0
Genetic Background	B6.Cg-Tcrb^tm1Mom Tg(SOD1*G93A)1Gur/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tcrb^tm1Mom mutation (12 available); any Tcrb mutation (94 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:143173 )

• accelerated disease progression

• shorter lifespans than Tg(SOD1*G93A)1Gur and Tg(SOD1*G93A)1Gur, Tcrb^tm1Mom heterozygous mice

growth/size/body

weight loss ( J:143173 )

• accelerated weight loss after disease onset compared to Tg(SOD1*G93A)1Gur, Tcrb^tm1Mom heterozygous littermates, mainly after day 135

nervous system

abnormal microglial cell physiology ( J:143173 )

• decreased microglia reactivity

motor neuron degeneration ( J:143173 )

• accelerated disease progression

• motor neuron loss in spinal cords earlier at day 140

• accelerated motor decline after disease onset compared to Tg(SOD1*G93A)1Gur, Tcrb^tm1Mom heterozygous littermates, mainly after day 135

immune system

abnormal microglial cell physiology ( J:143173 )

• decreased microglia reactivity

hematopoietic system

abnormal microglial cell physiology ( J:143173 )

• decreased microglia reactivity

Allelic Composition	Sirt2^tm1.2Auw/Sirt2^tm1.2Auw Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129 * C57BL/6 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt2^tm1.2Auw mutation (0 available); any Sirt2 mutation (25 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:194977 )

• as in Tg(SOD1*G93A)1Gur mice

nervous system

abnormal innervation pattern to muscle ( J:194977 )

• reduced innervation as in Tg(SOD1*G93A)1Gur mice

decreased neuron number ( J:194977 )

• as in Tg(SOD1*G93A)1Gur mice

abnormal action potential ( J:194977 )

• reduced compound action potential amplitudes as in Tg(SOD1*G93A)1Gur mice

Allelic Composition	Hdac6^tm1.1Pmt/Y Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hdac6^tm1.1Pmt mutation (0 available); any Hdac6 mutation (14 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

abnormal survival ( J:194977 )

• modest increase in survival compared with Tg(SOD1*G93A)1Gur mice

nervous system

abnormal innervation pattern to muscle ( J:194977 )

• NMJ innervation of the gastrocnemius muscle is improved compared to in Tg(SOD1*G93A)1Gur mice

increased neuron number ( J:194977 )

• in the ventral horn compared to in Tg(SOD1*G93A)1Gur mice with more pronounced protection of large neurons

abnormal action potential ( J:194977 )

• mice exhibit higher compound action potential amplitudes compared with Tg(SOD1*G93A)1Gur mice

behavior/neurological

decreased grip strength ( J:194977 )

• same age of onset as in Tg(SOD1*G93A)1Gur mice

Allelic Composition	Slc1a2^tm1Kta/Slc1a2⁺ Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc1a2^tm1Kta mutation (0 available); any Slc1a2 mutation (40 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:144898 )

• shortened lifespan (137 1.7 vs. 142 1.4 days)

cellular

abnormal cell physiology ( J:144898 )

• reduced glutamate transport in lumbar spinal cord at 120 days of age, compare with Tg(SOD1*G93A)1Gur mice

nervous system

decreased motor neuron number ( J:144898 )

• increase in the rate of motor decline accompanied by earlier motor neuron loss

• accelerated motor neuron loss at 120 days of age, compare with Tg(SOD1*G93A)1Gur mice

• significant declines occur between 105 and 120 days (42% reduction) and between 120 days and end stage, compared with between 120 days and endstage (56%) in Tg(SOD1*G93A)1Gur mice

Allelic Composition	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cx3cr1^tm1Litt mutation (6 available); any Cx3cr1 mutation (45 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:110266 )

• decreased survival in male mice compared with Tg(SOD1*G93A)1Gur mice

nervous system

decreased neuron number ( J:110266 )

• compared with Tg(SOD1*G93A)1Gur mice

behavior/neurological

decreased grip strength ( J:110266 )

• male mice exhibit a faster decline in hindlimb grip strength than Tg(SOD1*G93A)1Gur mice

growth/size/body

increased susceptibility to weight loss ( J:110266 )

• male mice exhibit a faster decline in body weight than Tg(SOD1*G93A)1Gur mice

Allelic Composition	Cnr1^tm1Map/Cnr1^tm1Map Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * ABH * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cnr1^tm1Map mutation (1 available); any Cnr1 mutation (43 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

extended life span ( J:111498 )

• despite similar disease progression, mice exhibit longer life span compared with Tg(SOD1*G93A)1Gur mice

Allelic Composition	Tg(SOD1*G93A)1Gur/0 Vegfa^tm2Pec/Vegfa^tm2Pec
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)
Vegfa^tm2Pec mutation (0 available); any Vegfa mutation (37 available)

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

mortality/aging

premature death ( J:84843 )

• die earlier (107 3 d) than Tg(SOD1*G93A)1Gur mice

muscle

muscle weakness ( J:84843 )

• worse muscle weakness than Tg(SOD1*G93A)1Gur mice

behavior/neurological

impaired coordination ( J:84843 )

• perform worse in the rotarod test (unable to stay for 2 min on the rotarod beyond 98 2 d) than Tg(SOD1*G93A)1Gur mice

Allelic Composition	Spi1^tm1Ram/Spi1^tm1Ram Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Spi1^tm1Ram mutation (0 available); any Spi1 mutation (27 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:116087 )

• mice receiving bone marrow from when treated with wild-type bone marrow transfer survive longer than Tg(SOD1*G93A)1Gur mice or mice receiving bone marrow transfers Tg(SOD1*G93A)1Gur mice but not as long as wild-type mice

nervous system

decreased motor neuron number ( J:116087 )

• motor neuron loss is more severe in mice receiving bone marrow transfer from Tg(SOD1*G93A)1Gur mice compared to mice receiving bone marrow transfers from wild-type mice that do not exhibit a significant amount of neuron loss

motor neuron degeneration ( J:116087 )

• antibiotic-treated mice receiving bone marrow cells from wild-type donors exhibit reduced motor neuron disease progression compared to those receiving bone marrow transplants from Tg(SOD1*G93A)1Gur mice

growth/size/body

growth/size/body region phenotype ( J:116087 )

N	• antibiotic-treated mice exhibit normal growth rates

Allelic Composition	Fgfbp1^tm1Gvdz/Fgfbp1^tm1Gvdz Tg(SOD1*G93A)1Gur/0 Tg(Thy1-YFP)16Jrs/0
Genetic Background	involves: 129S5/SvEvBrd * C57BL/6J * CBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fgfbp1^tm1Gvdz mutation (0 available); any Fgfbp1 mutation (18 available)
Tg(SOD1*G93A)1Gur mutation (4 available)
Tg(Thy1-YFP)16Jrs mutation (1 available)

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

mortality/aging

premature death ( J:237911 )

• accelerated in female and male mice compared with Tg(SOD1*G93A)1Gur mice

nervous system

abnormal neuromuscular synapse morphology ( J:237911 )

• fewer fully innervated neuromuscular junctions (NMJs) than in Tg(SOD1*G93A)1Gur mice with more partially and completely denervated NMJs

Allelic Composition	Mmp9^tm1Tvu/Mmp9^tm1Tvu Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * CD-1 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mmp9^tm1Tvu mutation (2 available); any Mmp9 mutation (49 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

mortality/aging ( J:141587 )

N	• mice survive 31% longer than Tg(SOD1*G93A)1Gur mice

nervous system

nervous system phenotype ( J:141587 )

N	• neuron loss observed in Tg(SOD1*G93A)1Gur mice is attenuated

immune system

decreased tumor necrosis factor secretion ( J:141587 )

• TNF-alpha staining is absent from neuronal cells in the spinal cord unlike in Tg(SOD1*G93A)1Gur mice

Allelic Composition	Tg(SOD1*G93A)1Gur/0 Tg(THY1-SNCA)1Sud/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)
Tg(THY1-SNCA)1Sud mutation (1 available)

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

nervous system

neurodegeneration ( J:115193 )

• mice display neurodegeneration similar to Dnajc5-null mice

Allelic Composition	Als2^tm1Deng/Als2^tm1Deng Tg(SOD1*G93A)1Gur/?
Genetic Background	involves: 129/Sv * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Als2^tm1Deng mutation (0 available); any Als2 mutation (88 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:129939 )

• all mice die of a neurodegenerative disorder by 150 days of age

nervous system

neurodegeneration ( J:129939 )

• mice display neurodegeneration similar to mice with just the Tg(SOD1*G93A)1Gur transgene

Allelic Composition	Faah^tm1Crv/Faah^tm1Crv Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129X1/SvJ * ABH * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Faah^tm1Crv mutation (0 available); any Faah mutation (26 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:111498 )

• similar to in Tg(SOD1*G93A)1Gur mice

muscle

abnormal muscle physiology ( J:111498 )

• mice exhibit increased muscle force and motor unit survival compared with Tg(SOD1*G93A)1Gur mice

nervous system

motor neuron degeneration ( J:111498 )

• mice exhibit less motor neuron degeneration compared with Tg(SOD1*G93A)1Gur mice

Allelic Composition	Dctn1^tm1Cai/Dctn1⁺ Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129X1/SvJ * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dctn1^tm1Cai mutation (0 available); any Dctn1 mutation (64 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

behavior/neurological

paralysis ( J:129269 )

• mice develop paralysis at the same rate as Tg(SOD1*G93A)1Gur mice

Allelic Composition	Bax^tm1Sjk/Bax^tm1Sjk Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bax^tm1Sjk mutation (1 available); any Bax mutation (24 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:111890 )

• live 14.6% longer than Tg(SOD1*G93A)1Gur mice

behavior/neurological

impaired coordination ( J:111890 )

• delayed onset of motor decline

• maintain 11 rpm on the rotarod for a longer period of their lifespan than Tg(SOD1*G93A)1Gur mice

nervous system

gliosis ( J:111890 )

• delayed reactive gliosis (P100 vs P40, compared with Tg(SOD1*G93A)1Gur mice)

abnormal motor neuron morphology ( J:111890 )

• atrophic axons of the lumbar motoneurons (MNs)

• the number of Slc18a3 mRNA-expressing MNs is not reduced in the entire lumbar spinal cord at the end-stage, compared with age-matched Bax^tm1Sjk homozygous controls

• many small groups of unmyelinated axons wrapped in glial cell processes in the end-stage fourth lumbar ventral root (L4 VR)

• higher levels of partially innervated synapses in end-stage delayed accumulation of mutant SOD1 in MNs (P40 vs P30, compared with Tg(SOD1*G93A)1Gur mice)

• delayed accumulation of mutant SOD1 in MNs (P40 vs P30, compared with Tg(SOD1*G93A)1Gur mice)

abnormal motor neuron innervation pattern ( J:111890 )

• decreased rate of neuromuscular denervation

• more medial gastrocnemii (MGs) axons and innervated

• neuromuscular junctions (NMJs) than Tg(SOD1*G93A)1Gur mutants at postnatal day 100 (P100)

• reduction of innervated synapses in the MG at P45, delayed onset compared with Tg(SOD1*G93A)1Gur mice

• contain more fully innervated NMJs at subsequent ages than Tg(SOD1*G93A)1Gur mutants, until P120

decreased motor neuron number ( J:111890 )

• delayed loss of both distal and proximal myelinated axons

• reduction of myelinated axons in end-stage MG nerve and L4 VR

cellular

abnormal mitochondrial morphology ( J:111890 )

• presence of vacuolated mitochondria in the ventral spinal cord at P25

• massive vacuolization in the lumbar ventral spinal cord at P100

Allelic Composition	Dync1h1^Cra1/Dync1h1⁺ Tg(SOD1*G93A)1Gur/?
Genetic Background	involves: C3HeB/FeJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dync1h1^Cra1 mutation (0 available); any Dync1h1 mutation (194 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:107901 )

• mice reach end stage by day 167 +/-2.5 SEM (standard error of measurement)

nervous system

astrocytosis ( J:107901 )

• astrocytosis is evident in the cervical and lumbar spinal cord

abnormal spinal cord morphology ( J:107901 )

• degeneration of the motor neurons in the cervical and lumbar spinal cord at end stage with astrocytosis and vacuolization

decreased motor neuron number ( J:107901 )

• degeneration of the motor neurons in the cervical and lumbar spinal cord is visible at end stage

motor neuron degeneration ( J:107901 )

• degeneration of the motor neurons in the cervical and lumbar spinal cord is visible at end stage

behavior/neurological

decreased locomotor activity ( J:107901 )

• motor activity is less than in Tg(SOD1*G93A)1Gur mice but does not deteriorate as quickly

growth/size/body

decreased body weight ( J:107901 )

• weight reduction was not as severe as in Tg(SOD1*G93A)1Gur mice

Allelic Composition	Tardbp^m1H/Tardbp⁺ Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C3H/HeH * C57BL/6 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tardbp^m1H mutation (1 available); any Tardbp mutation (60 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:211620 )

• as in Tg(SOD1*G93A)1Gur mice

muscle

decreased extensor digitorum longus weight ( J:211620 )

• compared with Tg(SOD1*G93A)1Gur mice

impaired muscle relaxation ( J:211620 )

• in the tibialis anterior compared with Tg(SOD1*G93A)1Gur mice

• however, relaxation time in the extensor digitorum longus is normal

abnormal muscle tone ( J:211620 )

• soft abdominal body tone as in Tardbp^m1H heterozygotes

behavior/neurological

decreased grip strength ( J:211620 )

• as in Tg(SOD1*G93A)1Gur mice

growth/size/body

decreased body weight ( J:211620 )

• as in Tg(SOD1*G93A)1Gur mice

nervous system

nervous system phenotype ( J:211620 )

N	• mice exhibit normal numbers of motor neurons in the sciatic motor pool

limbs/digits/tail

decreased extensor digitorum longus weight ( J:211620 )

• compared with Tg(SOD1*G93A)1Gur mice

Allelic Composition	Sod2^tm1Cje/Sod2⁺ Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6 * CD-1 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sod2^tm1Cje mutation (1 available); any Sod2 mutation (24 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:62381 )

• accelerated disease progression

• shorter lifespans than Tg(SOD1*G93A)1Gur mice

• mean decrease in survival is 11 days

behavior/neurological

impaired coordination ( J:62381 )

• worse motor performance in rotorod test than Tg(SOD1*G93A)1Gur mice starting from 106 days of age

nervous system

decreased substantia nigra size ( J:62381 )

• decreased number of total neurons within the substatia nigra at 110 days of age

abnormal motor neuron morphology ( J:62381 )

• microvesiculation within large ventral horn motor neurons at 90 days of age

decreased neuron number ( J:62381 )

• accelerated disease progression

• decreased number of total neurons within the ventral horns of the lumbar cord at 90 days of age

• greater neuronal loss than that in Tg(SOD1*G93A)1Gur mice at 110 days of age

decreased spinal cord ventral horn cell number ( J:62381 )

• decreased number of total neurons within the ventral horns of the lumbar cord starting at 90 days of age

• greater neuronal loss than that in Tg(SOD1*G93A)1Gur mice at 110 days of age

decreased spinal cord size ( J:62381 )

• atrophy of the lumbar spinal cord starting at 90 days of age

Allelic Composition	Tg(Myl1-Igf1)1Nros/0 Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myl1-Igf1)1Nros mutation (0 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:95812 )

• delayed the onset and in particular the progression of disease

• increase the survival by about 30 days to a maximal life span of 175 d

muscle

decreased skeletal muscle fiber diameter ( J:95812 )

• decreased muscle fiber diameter at 123 d and 150 d, compared with Tg(Myl1-Igf1)1Nros mice

• attenuated muscle atrophy, compared with Tg(SOD1*G93A)1Gur mice

centrally nucleated skeletal muscle fibers ( J:95812 )

• at all stages of disease, including at paralysis stage (123 d)

abnormal skeletal muscle fiber type ratio ( J:95812 )

• altered fiber type composition at 138 d with a shift toward a fast fiber type

nervous system

astrocytosis ( J:95812 )

• decrease in astroglial activation at paralysis stage (123 d) in the spinal cord, compared with Tg(SOD1*G93A)1Gur mice

decreased motor neuron number ( J:95812 )

• motor neuron loss is less severe at 112 and 123 d, compared with Tg(SOD1*G93A)1Gur mice

Allelic Composition	Tg(Gria2586N)238.2Rsp/0 Tg(SOD1G93A)1Gur/0
Genetic Background	involves: C57BL/6Ico

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Gria2*586N)238.2Rsp mutation (0 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:97818 )

• accelerated disease progression

• decreased survival (1932.93 vs. 208.45.06 days), compared with Tg(SOD1*G93A)1Gur mice

growth/size/body

weight loss ( J:97818 )

• declined body weight (14.3% over 51 days) after 20 weeks of age

behavior/neurological

impaired righting response ( J:97818 )

• lose righting reflex between 12 and 18 weeks

tremors ( J:97818 )

• accelerated onset (87.205.5 vs. 1856.3 days), compared with Tg(SOD1*G93A)1Gur mice

• in all 13 mice

Allelic Composition	Tg(SOD1*G93A)1Gur/0 Wld^s/Wld^s
Genetic Background	involves: C57BL/6J * C57BL/6Ola * SJL/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)
Wld^s mutation (1 available); any Wld mutation (2 available)

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

mortality/aging

premature death ( J:105092 )

• prolonged survival (140.335 vs. 131.13.7 days), compare with Tg(SOD1*G93A)1Gur mice

• female mice survive longer than the male (1455.1 vs. 1355.5 days)

Allelic Composition	Tg(SOD1*G93A)1Gur/0 Wld^s/+
Genetic Background	involves: C57BL/6J * C57BL/6Ola * SJL/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)
Wld^s mutation (1 available); any Wld mutation (2 available)

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

mortality/aging

premature death ( J:105092 )

• prolonged survival (141.98.9 vs. 131.13.7 days), compare with Tg(SOD1*G93A)1Gur mice

• female mice survive longer than the male (145.48.2 vs. 137.67.9 days)

nervous system

slow Wallerian degeneration ( J:105092 )

• 5 days after sciatic nerve transection, mice show delayed Wallerian degeneration, while Tg(SOD1*G93A)1Gur mice show a loss of axons and presence of myelin ovoids and phagocytes

abnormal motor neuron innervation pattern ( J:105092 )

• delayed denervation at the neuromuscular junction

• more axons and innervated neuromuscular junctions in nerve roots than Tg(SOD1*G93A)1Gur mutants at day 80

decreased motor neuron number ( J:105092 )

• similar levels of ventral root axon loss to that seen in Tg(SOD1*G93A)1Gur mice

decreased sensory neuron number ( J:105092 )

• similar levels of dorsal root axon loss to that seen in Tg(SOD1*G93A)1Gur mice

homeostasis/metabolism

slow Wallerian degeneration ( J:105092 )

• 5 days after sciatic nerve transection, mice show delayed Wallerian degeneration, while Tg(SOD1*G93A)1Gur mice show a loss of axons and presence of myelin ovoids and phagocytes

Allelic Composition	Bbc3^tm1Ast/Bbc3^tm1Ast Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6 * NZB * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bbc3^tm1Ast mutation (1 available); any Bbc3 mutation (18 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:130581 )

• despite the delay in disease progression, lifespan is similar to transgenic mice wild type for Bbc3

nervous system

gliosis ( J:130581 )

• gliosis and microglial activation in the spinal cord at 90 days of age are reduced compared to transgenic mice wild type for Bbc3

• however, by the end stage of the disease, gliosis and microglial activation are similar to transgenic mice wild type for Bbc3

motor neuron degeneration ( J:130581 )

• significant delay in motor neuron loss compared to transgenic mice wild type for Bbc3

• however, in older mice with end stage disease motor neuron loss in not different from transgenic mice wild type for Bbc3

behavior/neurological

behavior/neurological phenotype ( J:130581 )

N	• unlike transgenic mice wild type for Bbc3, no decrease in stride length is seen even at 120 days of age

decreased grip strength ( J:130581 )

• decline in paw grip endurance beginning at 98 days of age compared to 77 days of age in transgenic mice wild type for Bbc3

growth/size/body

weight loss ( J:130581 )

• body weight begins to significantly decrease at 105 days of age compared to 77 days of age in transgenic mice wild type for Bbc3

Allelic Composition	Tg(SOD1)2Gur/0 Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1)2Gur mutation (2 available)
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:109458 )

• lifespan is on average 117.7 days

nervous system

abnormal nervous system physiology ( J:109458 )

• mutants exhibit exacerbated amyotrophic lateral sclerosis-like phenotypes compared to single Tg(SOD1*G93A)1Gur mice, with onset of disease on average at 76.8 days of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:109458

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	B6.Cg-Tg(SOD1*G93A)1Gur

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:155140 )

• mean survivals in male and female mice are 153 2 and 161 2 days respectively

growth/size/body

decreased body weight ( J:155140 )

• decreased body weight starting at P65

behavior/neurological

tremors ( J:155140 )

• tremor onset occurred significantly sooner in male (912 days) compared to female (1002 days)

impaired coordination ( J:155140 )

• deficits in rotarod test

decreased grip strength ( J:155140 )

• deficits in paw grip endurance test (PaGE)

• delayed chronic deficits in female compared to male

decreased vertical activity ( J:155140 )

• decreased average locomotion velocity and rearing episodes

• significant motor deficits in male and female mice (at P45 and P65 respectively) in average locomotion velocity

• motor deficits in rearing episodes beginning at P45

• persist at each subsequent time point up to and beyond the onset of overt clinical symptoms

• deficits in all four open-field performance measures start earlier than the conventional PaGE or rotarod tests

• delayed chronic deficits in average velocity in female compared to male

decreased locomotor activity ( J:155140 )

• motor deficits in ambulatory distance and resting time in male mice beginning at P45

• transient or no deficits in ambulatory distance and rest behaviors, respectively in female

muscle

decreased skeletal muscle size ( J:155140 )

• smaller hindlimb calf girth dorsal/ventral (d/v) starting at P55

• smaller hindlimb calf girth medial/lateral starting at P65

• smaller hindlimb thigh girth medial/lateral starting at P75

• calf (d/v) and thigh muscle girth are able to predict genotype in pre-symptomatic animals with 80% or greater accuracy (about 40 day prior to tremor onset)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:155140

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	B6.Cg-Tg(SOD1*G93A)1Gur/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:95812 , J:115355 , J:128550 , J:138237 , J:211734 )

• disease onset at 111+/-1.8 days (J:95812)

• die within 10+/-0.6 days of clinical disease onset (J:95812)

• maximal life span of 145 days (J:95812)

• mean time from onset of tremors to death is 16.5 +/-9.3 days (J:115355)

• Background Sensitivity: increased survival on C57BL/6J background (50% survival at 157.1+/-9.3 days) in contrast to B6SJL background (50% survival at 128.9+/-9.1 days) (J:115355)

• Background Sensitivity: increased survival on C57BL/6J background (143.6+/-7.5 days) in contrast to B6SJL/J background (130.2+/-11.2 days) (J:128550)

• survive from 19-22 weeks (J:138237)

• increased survival by weekly immunization with Copolymer-1 (9.9%) in female mice (J:138237)

• reconstitution with polyclonal-activated Treg and Teff subsets delays loss of motor function and extends survival (J:138237)

• reconstitution with Treg delays neurological symptom onset (J:138237)

• reconstitution with Teff increases latency between disease onset and entry into late stage (J:138237)

• average lifespan is 171.8 days (J:211734)

behavior/neurological

tremors ( J:115355 , J:138237 )

• observed hindlimb tremors when suspended by tail at 142.3 +/- 10.6 days (approx. 20 weeks) (J:115355)

• hind limb tremors at 14 weeks of age (J:138237)

impaired coordination ( J:211734 )

• mice show impaired performance on the rotarod and in hanging from a grid

abnormal gait ( J:115355 )

• exhibited longer stride and stance times as compared to C57BL/6J controls, however swing time difference was not significant

long stride length ( J:138237 )

muscle

decreased skeletal muscle fiber diameter ( J:95812 )

• at 112 d and 123 d compared with wild-type mice

• severe muscle atrophy at 123 d

abnormal skeletal muscle fiber type ratio ( J:95812 )

• altered fiber type composition at 80 d with a shift toward a fast fiber type

nervous system

decreased motor neuron number ( J:95812 )

• progressive reduction in the number of motor neuron from clinical onset to end-stage disease

• a reduction of 37 and 55% in the number of motor neurons at clinical onset (112 d) and at end-stage disease (123 d), respectively

motor neuron degeneration ( J:211734 )

• average onset of motor neuron degeneration is 137.4 days

immune system

abnormal spleen morphology ( J:138237 )

• diminished follicular area by 67% with a greater number (41%) of follicles at end stage

decreased spleen weight ( J:138237 )

• reduced spleen weight (59%) at 22 weeks of age

decreased splenocyte number ( J:138237 )

• reduced viable spleen cell numbers (70%) at 22 weeks of age

abnormal T cell physiology ( J:138237 )

• progressively diminished proliferative capacity of T cells with age

hematopoietic system

abnormal spleen morphology ( J:138237 )

• diminished follicular area by 67% with a greater number (41%) of follicles at end stage

decreased spleen weight ( J:138237 )

• reduced spleen weight (59%) at 22 weeks of age

decreased splenocyte number ( J:138237 )

• reduced viable spleen cell numbers (70%) at 22 weeks of age

abnormal T cell physiology ( J:138237 )

• progressively diminished proliferative capacity of T cells with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:211734

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	B6SJL-Tg(SOD1*G93A)1Gur

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

nervous system

abnormal neuron morphology ( J:144199 )

• about 20% lower glycinergic synapses (GlyT2-boutons) densities on lumbar spinal motoneurons in asymptomatic 8-week-old mice

• the density of GlyT2-boutons shows a slight recovery at 10 weeks of age compared with 8-week-old transgenic mice

• the number of GlyT2-boutons is reduced further at 12 and 14 weeks of age

• majority of GlyT2-boutons is lost at 16 weeks of age

• decreased number of Renshaw cells at 12 and 14 weeks of age

abnormal cholinergic neuron morphology ( J:144199 )

• decreased density of ChAT-boutons at 16 weeks of age

abnormal dendrite morphology ( J:149044 )

• reduction in dendrite length and branch nodes on basal dendrites of prelimbic/infralimbic medial prefrontal cortex neurons

• smaller diameter of basal dendrites on branch order one

abnormal dendritic spine morphology ( J:149044 )

• decreased spine density on basal dendrite segments of branch order four

abnormal spinal cord morphology ( J:144199 )

• cytoplasmic vacuoles in some motoneuron cell bodies and proximal dendrites in lumbar spinal cord at 10 weeks of age

• more apparent cytoplasmic vacuoles in motoneurons and more motoneurons possessed vacuoles at 12 weeks of age

abnormal motor neuron morphology ( J:144199 )

• cytoplasmic vacuoles starting at 10 weeks of age

• swollen, degenerating axons with segmental enlargements in the ventral horn neuropil and white matter starting at 10 weeks of age

• the residual motoneurons tend to be smaller than that the typical alpha-motoneurons at 16 weeks of age

• the average size of motoneurons gradually increases from 10 weeks of age and reaches maximum at 12 weeks

• decreased number of mid-size (20-30 micrometer) motoneurons at 14 weeks of age

decreased motor neuron number ( J:144199 )

• decreased number of motoneurons at 14 weeks of age

• the number of motoneurons is reduced further at 16 weeks of age

motor neuron degeneration ( J:144199 )

• swollen, degenerating axons with segmental enlargements in the ventral horn neuropil at 10 weeks of age

• decreased number of motoneurons at 14 weeks of age

• the number of motoneurons is reduced further at 16 weeks of age

abnormal spinal cord interneuron morphology ( J:144199 )

• about 20% lower GlyT2-boutons densities on lumbar spinal motoneurons in asymptomatic 8-week-old mice

• the density of GlyT2-boutons shows a slight recovery at 10 weeks of age compared with 8-week-old transgenic mice

• the number of GlyT2-boutons is reduced further at 12 and 14 weeks of age

• majority of GlyT2-boutons is lost at 16 weeks of age

• decreased density of ChAT-boutons at 16 weeks of age

abnormal ventral interneuron 1 morphology ( J:149044 )

• decreased number of Renshaw cells at 12 and 14 weeks of age

abnormal spinal cord ventral horn morphology ( J:144199 )

• swollen, degenerating axons with segmental enlargements in the ventral horn neuropil at 10 weeks of age

abnormal spinal cord white matter morphology ( J:144199 )

• swollen, degenerating axons with segmental enlargements in the white matter at 10 weeks of age

cellular

abnormal mitochondrial morphology ( J:144199 )

• vacuoles in large swollen mitochondria in the cell bodies and proximal dendrites of some motoneurons and in dendrites within in the neuropil at 10 weeks of age

• fulminant mitochondrial swelling at 12 weeks of age

behavior/neurological

abnormal fear-related response ( J:149044 )

• impaired extinction of conditioned fear

• a stronger amount of freezing and run a shorter distance in comparison with wild-type following the three tone alone presentations on day 3

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:144199

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

Structural and functional defects of mitochondria in Tg(SOD1*G93A)1Gur/0 muscle

mortality/aging

premature death ( J:103582 , J:128550 , J:138237 , J:146652 )

• survival is 157.2 2.2 days (J:103582)

• Background Sensitivity: decreased survival on SJL/J background (119.29.7 days) in contrast to B6SJL/J background (130.211.2 days) (J:128550)

• female mice survive longer than the male on B6SJL/J (132.812.4 vs. 127.99.5 days) and SJL/J (122.510.9 vs. 115.26.2 days) background (J:128550)

• survive from 16-20 weeks (J:138237)

• survival in male mice ranges between 105 days and 127 days (J:146652)

behavior/neurological

abnormal drinking behavior ( J:130811 )

• progressive decrease in lick rhythm over time beginning at approximately 102 days of age

increased anxiety-related response ( J:110437 )

• reduced mean time spent in the center of the open field from 4 months on

• slightly increased anxiety-related behavior

abnormal motor capabilities/coordination/movement ( J:130811 )

tremors ( J:138237 , J:146652 )

• hind limb tremors at 14 weeks of age (J:138237)

• mild hindlimb tremor at 90 days of age (J:146652)

impaired coordination ( J:130811 )

• lower performance rate (<90%) in rotarod test from 71 days of age

• failed rotarod test after 113 days of age

decreased grip strength ( J:103582 , J:130811 )

• reduced muscle strength in this traction test even from the age of 35 days (J:103582)

• progressive reduced forelimb and hindlimb grip force from the onset of testing (64 days of age) (J:130811)

decreased locomotor activity ( J:110437 )

• progressively decreased overall motor activity during the first 3 months

• lower horizontal travel distance and number of stops at 3.5 months of age in open field analysis

• longer duration of stops at 3.5-4.5 months of age

hindlimb paralysis ( J:110437 , J:146652 )

• first signs of hindlimb paralysis at 3.5-5 months of age (J:110437)

• dragging in one hindlimb and inability to grasp a cage bar at 103 days of age (J:146652)

• paralysis progresses to both hindlimbs within 3-4 days (J:146652)

nervous system

abnormal microglial cell morphology ( J:143173 , J:165019 )

• increased cell size starting at day 100 (J:143173)

• increased granularity starting at day 100 (J:143173)

• large vacuoles in microglial cell cytoplasm in the cervical and lumbar spinal cord (J:165019)

microgliosis ( J:110437 , J:143173 , J:146652 , J:165019 )

• appear simultaneously to the degenerative changes and increase substantially with time (J:110437)

• microglia (CD11b+ CD45lo) population expanded 1.65-fold by day 135 in spinal cords (J:143173)

• increase in the number of glial processes abutting onto the neuronal surface and apposed to the presynaptic terminal in 10-week-old and 18-week-old mice (J:146652)

• first noted at 6 weeks (J:146652)

• some microglial cells occupy areas where formerly occupied by astrocytes or oligodendrocytes in the cervical and lumbar spinal cord (J:165019)

abnormal brain morphology ( J:110437 )

• degenerating somata in the brain at 4 months of age

abnormal brainstem morphology ( J:110437 , J:127265 )

• swollen neurites and vacuoles in the brainstem affecting cerebellar and various motor nuclei (the hypoglossal, the ambiguus and the facial nucleus) within the following month (J:110437)

• vacuoles in the trigeminal nucleus and the locus coeruleus neuropil at 3 months of age (J:110437)

• degeneration of brainstem motor nuclei (the trigeminal, hypoglossal and facial nucleus as early as Day 80 by magnetic resonance imaging (MRI) (J:127265)

• higher relaxation parameter T2 values for all the three brainstem nuclei after 80 days (J:127265)

• continuous age-dependent T2 values increase (J:127265)

• increased area of the brainstem nuclei (hypoglossal and facial nucleus) between 80 and 120 days after birth (J:127265)

• H&E staining with brain sections show same morphological alterations (J:127265)

• increased number of vacuoles in the brainstem nuclei from Day 80 onwards (J:127265)

• continuous age-dependent increased number of vacuoles (J:127265)

abnormal midbrain morphology ( J:110437 )

• degeneration lesions in the retrorubral field

abnormal superior colliculus morphology ( J:110437 )

• degeneration lesions in the deep layers of the colliculi superior

abnormal oculomotor nucleus morphology ( J:110437 )

• heavily filled with Gallyas+, coiled and ballooned axonal and dendritic profiles in the oculomotor ,the trochlear nucleus at 4 months of age

abnormal substantia nigra morphology ( J:110437 )

• degeneration lesions in the substantia nigra

abnormal tegmentum morphology ( J:110437 )

• degeneration lesions in the neuropil of the ventral tegmental field

abnormal red nucleus morphology ( J:110437 )

• spongio-form degenerative changes in the red nucleus

abnormal globus pallidus morphology ( J:110437 )

• degenerative changes in the globus pallidus at 5 months of age

abnormal hypothalamus morphology ( J:110437 )

• degenerative changes in the hypothalamic nuclei at 5 months of age

abnormal thalamus morphology ( J:110437 )

• degeneration lesions in the nucleus anterior thalami

abnormal cerebral cortex morphology ( J:110437 )

• degenerative pyramidal-shaped neurons and several long neurites in motor as well as in extra-motor areas of the cerebral cortex at 5 months of age

brain vacuoles ( J:110437 , J:127265 )

• vacuolization in the brain and reach telencephalic regions at 5 months of age (J:110437)

• increased number of vacuoles in the brainstem nuclei from Day 80 onwards (J:127265)

• continuous age-dependent increased number of vacuoles (J:127265)

abnormal astrocyte morphology ( J:165019 )

• swollen, progressive degeneration of astrocytes in the brainstem, cervical and lumbar spinal cord

• characterized by mitochondrial damage, cellular edema and cell rupture

astrocytosis ( J:110437 )

• appear simultaneously to the degenerative changes and increase substantially with time

abnormal corticospinal tract morphology ( J:133155 )

• progressive loss of corticospinal tract neurons (9% at 60 days, 30% at 90 days and 53% at 110 days)

• progressive loss of dorsal corticospinal axons (13% at 60 days, 22% at 90 days and 32% at 110 days)

abnormal synaptic bouton morphology ( J:146652 )

• degenerative changes occurred in all classes of terminal at 6, 10 and 18 weeks of age, apart from the C-type terminal

• thin glial processes either partly or totally engulfed some terminals at 18 weeks of age

• reduction in both terminal number and coverage of the somal membrane, and decline further by around 60% at 18 weeks of age

• increase in the proportional numbers of C-terminals at 6 and 18 weeks of age

• increase in the membrane coverage of C-terminals at 6, 10 and 18 weeks of age

• progressive enlargement of the C-terminal presynaptic terminal at 10 and 18 weeks of age

• increased size of the postsynaptic structure of C-terminals

• increased length of the subsynaptic cistern of C-terminals

• increased number of the Nissl body rER lamellae of C-terminals at 18 weeks of age

• increased overall length of the Nissl body rER lamellae of C-terminals at 10 and 18 weeks of age

abnormal spinal cord morphology ( J:110437 , J:143173 )

• swollen neurites and vacuoles of various dimensions and large neuritic spheroids in some spinal motor neurons at the age of 2 months (J:110437)

• restricted to the ventral horns of spinal cords at the age of 2 months (J:110437)

• increase and extend into the dorsal horn of the spinal cord within the following month (J:110437)

• increased lymphocyte population in spinal cords at day 65 (J:143173)

• increase with disease progression, 36-fold by day 135 (J:143173)

• significant accumulation of CD4+ and CD8+ T cells in spinal cords (J:143173)

• natural killer cell in spinal cords (J:143173)

abnormal motor neuron morphology ( J:129976 , J:146652 , J:165019 , J:212250 )

• decreased mitochondria in axonal mitochondria (J:129976)

• increased intermitochondrial distance by 30-50% in axons (J:129976)

• increased mitochondria in cell bodies of motoneurons (J:129976)

• paler and more strongly stained motoneurons, with vacuolation in the more strongly stained motoneurons by 6 weeks (J:146652)

• more electron-lucent than electron-dense motoneurons by 18 weeks, and many motoneurons exhibit extensive vacuolation (J:146652)

• large membrane bound vacuoles consisting of either dilated axons or dendrite (J:165019)

• mitochondria with swollen cristae in both axons and dendrites near capillaries (J:165019)

• most ventral horn motor neurons lack autofluorescent lipofuscin in cell bodies at 3 months of age (J:212250)

• however, lipofuscin is detected in the neuron cell bodies of the dorsal regions of the spinal cord gray matter (J:212250)

decreased motor neuron number ( J:133155 )

• progressive loss of upper motor neurons

• small loss of corticospinal (9%), bulbospinal (12%) and rubrospinal (14%) projections at 60 days

• loss of 30% of corticospinal, 33% of bulbospinal and 33% of rubrospinal neurons at 90 days

• loss of 53% of corticospinal, 41% of bulbospinal and 43% of rubrospinal neurons at 110 days

motor neuron degeneration ( J:110437 , J:165019 )

• vacuolization and silver-impregnated neurites at 2 months of age in the spinal cord, proceed caudocranially into the brain and reach telencephalic regions at 5 months of age (J:110437)

• swollen and degenerating motor neurons in the late stage in the brainstem, cervical and lumbar spinal cord (J:165019)

• intracellular edema in some motor neurons, characterized by cytoplasmic enlargement (J:165019)

abnormal spinal cord ventral horn morphology ( J:212250 )

• most ventral horn motor neurons lack autofluorescent lipofuscin in cell bodies at 3 months of age

abnormal nervous system physiology ( J:111280 )

• lower basal ATP levels in cerebral cortex in 30-day-old mice

• the extent of impairment in ATP production progresses with age

• partially ameliorated by creatine administration

• reduced ADP levels by 60 days of age

• reduced creatine levels by 90 days of age in both cerebral cortex and spinal cord

CNS inflammation ( J:110437 )

• lymphocytes and CD11c positive dendritic cells infiltrate the affected CNS regions not before 4 months of age

• first in the spinal cord, predominantly in the white matter

• later in the degenerating regions up to the mesencephalon

abnormal axonal transport ( J:129976 )

• increased number of retrograde mitochondria by around 80% after fast axonal transport (FAT)

• decreased fraction of anterograde mitochondria

cellular

abnormal endoplasmic reticulum morphology ( J:146652 , J:165019 )

• Nissl body rough ERs (rER) in the terminals appear more prominent, with evidence of polyribosomal hyperplasia at 10 weeks of age (J:146652)

• dilated Golgi-ER and less organized, with increased numbers of separated highly dilated ER profiles (J:146652)

• rER damage appearing as 'splits' in the cytoplasm by 18 weeks (J:146652)

• dilation of the endoplasmic reticulum in motor neuron cytoplasm in the brainstem, cervical and lumbar spinal cord (J:165019)

abnormal mitochondrial morphology ( J:165019 )

• characterized by swelling, cristae disruption and eventual vacuolization of mitochondria

• disorganized mitochondrial cristae and degenerating mitochondria in astrocytes, capillary endothelial cells and neuropil in the brainstem, cervical and lumbar spinal cord

abnormal mitochondrial crista morphology ( J:146652 )

• reduced numbers of short, 'broken' cristae in the terminals at 10 weeks of age

abnormal mitochondrial shape ( J:129976 )

• lower aspect ratio showing rounding up mitochondria

increased mitochondrial size ( J:158298 )

• enlarged mitochondria with vacuoles, invading the sarcomeric A band

dilated mitochondrion ( J:146652 )

• swollen mitochondria

abnormal cell physiology ( J:103582 , J:129976 )

• decreased glutamate uptake in synaptosomes at 150 days of age (J:103582)

• decreased anterograde frequency by almost 60% for the activity of mitochondrial molecular motors (J:129976)

• decreased velocity of anterograde transport (J:129976)

• reduced persistence of movement in the anterograde direction (J:129976)

• normal retrograde frequency (J:129976)

• normal overall level of activity of mitochondrial molecular motors (J:129976)

• normal velocity of retrograde transport (J:129976)

abnormal mitochondrial physiology ( J:158298 )

• loss of mitochondrial inner membrane potential in fiber segments near the neuromuscular junction starting at the age of 37 days

abnormal respiratory electron transport chain ( J:129976 )

• reduced mitochondrial electron transport activity

homeostasis/metabolism

edema ( J:165019 )

• progressive edema in the brainstem, cervical and lumbar spinal cord

• characterized by the formation of protein-filled areas in the extracellular space formerly occupied by astrocytes or neuropil

abnormal glucose homeostasis ( J:111280 )

• impaired glucose utilization rates in multiple brain components of the motor system as early as 60 days of age

• components of the bulbospinal projection pathway are compromised by 60 days of age, whereas rubrospinal projections become involved later

• reductions in glucose use in the gray matter of cervical, thoracic, or lumbar regions of the spinal cord in 120-day-old mice

abnormal calcium ion homeostasis ( J:158298 )

• greater osmotic stress-induced Ca²⁺ release activity in fiber segments with depolarized mitochondria

muscle

abnormal skeletal muscle fiber morphology ( J:158298 )

• enlarged mitochondria with vacuoles, invading the sarcomeric A band

abnormal muscle physiology ( J:158298 )

• greater osmotic stress-induced Ca²⁺ release activity in fiber segments with depolarized mitochondria

muscle weakness ( J:130811 )

• progressive decrease in tongue force beginning at approximately 113 days of age

• progressive reduced forelimb and hindlimb grip force from the onset of testing (64 days of age)

progressive muscle weakness ( J:103582 , J:146652 )

• after 120 days of age (J:103582)

• dragging in one hindlimb and inability to grasp a cage bar at 103 days of age (J:146652)

• paralysis progresses to both hindlimbs within 3-4 days (J:146652)

immune system

increased basophil cell number ( J:129215 )

• increased basophil number compared with Tg(SOD1)2Gur mice

decreased leukocyte cell number ( J:129215 )

• reduced WBC numbers

• normal neutrophil levels

decreased eosinophil cell number ( J:129215 )

• decreased number of circulating eosinophils

decreased monocyte cell number ( J:129215 )

• decreased number of circulating monocytes

abnormal lymphocyte morphology ( J:129215 )

• a number of lymphocytes spontaneously form rosettes with autologous erythrocytes in two thirds of the mice

decreased lymphocyte cell number ( J:129215 )

• lower lymphocyte density

abnormal microglial cell morphology ( J:143173 , J:165019 )

• increased cell size starting at day 100 (J:143173)

• increased granularity starting at day 100 (J:143173)

• large vacuoles in microglial cell cytoplasm in the cervical and lumbar spinal cord (J:165019)

microgliosis ( J:110437 , J:143173 , J:146652 , J:165019 )

• appear simultaneously to the degenerative changes and increase substantially with time (J:110437)

• microglia (CD11b+ CD45lo) population expanded 1.65-fold by day 135 in spinal cords (J:143173)

• increase in the number of glial processes abutting onto the neuronal surface and apposed to the presynaptic terminal in 10-week-old and 18-week-old mice (J:146652)

• first noted at 6 weeks (J:146652)

• some microglial cells occupy areas where formerly occupied by astrocytes or oligodendrocytes in the cervical and lumbar spinal cord (J:165019)

abnormal spleen morphology ( J:138237 )

• diminished follicular architecture with a greater number of follicles at end stage

small spleen ( J:138237 )

• reduced spleen size at end stage (20-22 weeks of age)

decreased spleen weight ( J:138237 )

• reduced spleen weight (45%) at 19 weeks of age

abnormal splenic cell ratio ( J:138237 )

• decreased levels of CD45RA+ (naive) T cells

• increased levels of CD45RO+ (memory) T cells

abnormal splenocyte morphology ( J:138237 )

• increased annexin-V associated apoptosis and necrosis of lymphocytes at pre-symptomatic stage (14 weeks of age)

CNS inflammation ( J:110437 )

• lymphocytes and CD11c positive dendritic cells infiltrate the affected CNS regions not before 4 months of age

• first in the spinal cord, predominantly in the white matter

• later in the degenerating regions up to the mesencephalon

growth/size/body

slow postnatal weight gain ( J:130811 )

• no weight gain beginning at approximately 108 days of age

cardiovascular system

abnormal vascular endothelial cell morphology ( J:165019 )

• characterized by mitochondrial damage, swelling of endoplasmic reticulum, cytoplasmic vacuolization and cell death

• endothelial cell membrane and/or basement membrane damage, followed by vascular leakage

• progressive swollen and degenerating capillary endothelial cells in the brainstem, cervical and lumbar spinal cord

abnormal capillary morphology ( J:165019 )

• disruption of blood-brain barrier and blood-spinal cord barrier in areas of motor neuron degeneration in the brainstem, cervical and lumbar spinal cord

• pericytes under the capillary basement membrane

• intracellular edema, endoplasmic reticulum swelling and formation of numerous large vacuoles in capillary endothelial cells cytoplasm

• multiple layers of endothelial cells separated by sheets of basement membrane material

hematopoietic system

increased basophil cell number ( J:129215 )

• increased basophil number compared with Tg(SOD1)2Gur mice

decreased leukocyte cell number ( J:129215 )

• reduced WBC numbers

• normal neutrophil levels

decreased eosinophil cell number ( J:129215 )

• decreased number of circulating eosinophils

decreased monocyte cell number ( J:129215 )

• decreased number of circulating monocytes

abnormal lymphocyte morphology ( J:129215 )

• a number of lymphocytes spontaneously form rosettes with autologous erythrocytes in two thirds of the mice

decreased lymphocyte cell number ( J:129215 )

• lower lymphocyte density

abnormal microglial cell morphology ( J:143173 , J:165019 )

• increased cell size starting at day 100 (J:143173)

• increased granularity starting at day 100 (J:143173)

• large vacuoles in microglial cell cytoplasm in the cervical and lumbar spinal cord (J:165019)

microgliosis ( J:110437 , J:143173 , J:146652 , J:165019 )

• appear simultaneously to the degenerative changes and increase substantially with time (J:110437)

• microglia (CD11b+ CD45lo) population expanded 1.65-fold by day 135 in spinal cords (J:143173)

• increase in the number of glial processes abutting onto the neuronal surface and apposed to the presynaptic terminal in 10-week-old and 18-week-old mice (J:146652)

• first noted at 6 weeks (J:146652)

• some microglial cells occupy areas where formerly occupied by astrocytes or oligodendrocytes in the cervical and lumbar spinal cord (J:165019)

abnormal spleen morphology ( J:138237 )

• diminished follicular architecture with a greater number of follicles at end stage

small spleen ( J:138237 )

• reduced spleen size at end stage (20-22 weeks of age)

decreased spleen weight ( J:138237 )

• reduced spleen weight (45%) at 19 weeks of age

abnormal splenic cell ratio ( J:138237 )

• decreased levels of CD45RA+ (naive) T cells

• increased levels of CD45RO+ (memory) T cells

abnormal splenocyte morphology ( J:138237 )

• increased annexin-V associated apoptosis and necrosis of lymphocytes at pre-symptomatic stage (14 weeks of age)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:133155 , J:143173 , J:146652 , J:212250

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: ABH * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:111498 )

• Background Sensitivity: mice on a background containing ABH exhibit shorter life span than mice on a mixed C57BL/6 and SJL background

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6 * CD-1 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

nervous system

decreased substantia nigra size ( J:62381 )

• decreased number of total neurons within the substatia nigra at 110 days of age

decreased neuron number ( J:62381 )

• decreased number of total neurons within the ventral horns of the lumbar cord at 110 days of age

decreased spinal cord ventral horn cell number ( J:62381 )

• decreased number of total neurons within the ventral horns of the lumbar cord at 110 days of age

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6Ico

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:97818 )

• decreased survival (208.45.06 vs. >350 days), compared with wild-type mice

growth/size/body

weight loss ( J:97818 )

• declined body weight (12% over 64 days) after 20 weeks of age

behavior/neurological

tremors ( J:97818 )

• onset at 1856.3 days

• in only 3 of 11 mice

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6J * C57BL/Ola * SJL/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:105092 )

• mice reach end stage by day 131.13.7

nervous system

decreased sensory neuron number ( J:105092 )

• lose 53% of total dorsal root axons by day 80

Allelic Composition	Tg(SOD1*G93A)1Gur/0
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

Presence of neurofilament spheroids in the spinal cord of an 82-day old Tg(SOD1)2Gur/0 mouse

mortality/aging

premature death ( J:84843 , J:109423 , J:109458 , J:115355 , J:130581 )

• die after 124 4 days (J:84843)

• die within 7-10 days after paralysis (J:109423)

• Background Sensitivity: increased survival on C57BL/6J background (50% survival at 157.1+/-9.3 days) in contrast to B6SJL background (50% survival at 128.9+/-9.1 days) (J:115355)

growth/size/body

decreased body weight ( J:91800 )

• lower body mass

weight loss ( J:130581 )

• body weight begins to significantly decrease at 77 days of age

nervous system

gliosis ( J:55026 , J:130581 )

• resting microglial cells in the white matter of the spinal cord (J:55026)

• reactive microglial cells in the gray matter of the spinal cord at 117 and165 days of age (J:55026)

• using MAC-1 and F4/80 as specific markers of microglial cells (J:55026)

• gliosis and microglial activation are seen in the spinal cord by 90 days of age (J:130581)

astrocytosis ( J:55026 , J:76718 )

• resting astrocytes in the white matter of the spinal cord at both the cervical and lumbar levels (J:55026)

• reactive astrocytes in the gray matter of the spinal cord at 117 and165 days of age, predominated in the anterior horn of the spinal cord (J:55026)

• using GFAP as a specific marker of astrocytes (J:55026)

• exhibit astrocytosis in spinal cord, mainly in the anterior and lateral horns (J:76718)

abnormal spinal cord morphology ( J:76718 )

• exhibit neurofilament-rich spheroids at 82-days of age, similar to those seen in human amyotrophic lateral sclerosis; other neuronal intermediate filament proteins (alpha-internexin, peripherin) also accumulate in the spheroids

• more spheroids are seen in cervical and thoracic regions compared to lumbar and sacral spinal cord in early symptomatic mutants, however similar numbers at all spinal cord levels are seen in older mutants

• spheroids are more frequently found in the anterior horn and in the anterior and lateral columns of the white matter than in the posterior horn

• exhibit thickened dystrophic neurites filled with immunoreactive neurofilament-rich inclusions

abnormal motor neuron morphology ( J:111890 )

• mutant SOD1-positive inclusions in the ventral horn starting at P30

• the number of motoneurons with aggregates decreased dramatically over time

decreased motor neuron number ( J:84843 )

• motoneuron loss beyond 3 months of age

motor neuron degeneration ( J:76718 , J:130581 )

• develop motor neuron disease; exhibit degenerating motor neurons filled with perikaryal vacuoles in the anterior and lateral horns (J:76718)

• significant decrease in sciatic motor neuron survival by 90 days of age (J:130581)

abnormal nervous system physiology ( J:109458 )

• mutants develop amyotrophic lateral sclerosis-like disease, with onset of disease on average at 103.2 days

increased cerebral infarct size ( J:61249 )

• increased infarct volume at 24 hours after transient focal cerebral ischemia

abnormal neuron physiology ( J:130581 )

• increased expression of unfolded protein response target genes by 50 days of age in motor neurons

impaired synaptic plasticity ( J:109423 )

• abnormal corticostriatal synaptic plasticity between postnatal days 100 and 110

abnormal CNS synaptic transmission ( J:109423 )

abnormal excitatory postsynaptic potential ( J:109423 )

• intracellular recordings of single excitatory postsynaptic potentials from striatal medium spiny neurons showing an LTP, instead of an LTD

abnormal long-term potentiation ( J:109423 )

• a tetanic stimulation induced a long term potential (LTP), instead of an long term depression (LTD) in field potentials induced in the striatum following corticostriatal pathway stimulation

reduced long-term depression ( J:109423 )

• in the presence of the N-methyl-D-aspartic acid (NMDA) receptor antagonist AP5, repetitive stimulation of the corticostriatal pathway results in LTD

• the degree of field-amplitude depression is smaller in the presence of the NMDA receptor antagonist AP5

• exogenous dopamine (DA) restores LTD

• the presence of the selective DA D2 receptor agonist restores LTD

abnormal paired-pulse inhibition ( J:109423 )

• trend towards less susceptible to paired-pulse depression

behavior/neurological

abnormal active avoidance behavior ( J:109423 )

• less conditioned responses

• less increased performance as training proceeds

• normal minimal foot-shock intensity eliciting vocalization

abnormal motor capabilities/coordination/movement ( J:76718 )

• the first signs of motor neuron disease, hyperflexia, crossed spread of spinal reflexes, and shaking of the limbs when suspended in the air, occur by 91 days of age

impaired coordination ( J:84843 )

• unable to stay for 2 min on the rotarod beyond 118 4 days of age

decreased grip strength ( J:130581 )

• steady decline in paw grip endurance beginning at 77 days of age

abnormal locomotor behavior ( J:109423 )

• locomotor activity decreases more rapidly across 5 sessions

abnormal gait ( J:130581 )

• impairment in walking patterns with reduced stride length beginning at 90 days of age

short stride length ( J:130581 )

• beginning at 90 days of age

paralysis ( J:76718 , J:109423 )

• end-stage disease occurs at an average of 136 days, with mutants exhibiting severe paralysis and inability to forge for food or water (J:76718)

• develop paralysis rapidly after signs of hindlimb weakness (J:109423)

hindlimb paralysis ( J:76718 )

• develop a progressive worsening paresis involving primarily the hind limbs with atrophy of the skeletal musculature

muscle

skeletal muscle atrophy ( J:76718 )

• develop atrophy of skeletal musculature

abnormal muscle physiology ( J:111498 )

• mice exhibit decreased muscle tetanic force compared with wild-type mice

• mice exhibit reduced survival of motor units compared with wild-type mice

• the extensor digitorum longus exhibits fatigue resistance compared with wild-type muscles

muscle weakness ( J:84843 , J:109423 )

• severe muscle weakness beyond 3 months of age (J:84843)

• hindlimb weakness from 4 months of age (J:109423)

adipose tissue

abnormal adipose tissue morphology ( J:91800 )

• exhibit reduced adipose tissue accumulation

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

homeostasis/metabolism

abnormal circulating hormone level ( J:91800 )

increased circulating corticosterone level ( J:91800 )

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 nitric oxide homeostasis ( J:55026 )

• increased spinal cord iNOS activity at 117 and 165 days of age

• decreased spinal cord nNOS activity at 165 days of age

increased oxygen consumption ( J:91800 )

• exhibit higher rates of total oxygen consumption

increased cerebral infarct size ( J:61249 )

• increased infarct volume at 24 hours after transient focal cerebral ischemia

cellular

abnormal cell physiology ( J:61249 )

• decreased glutamate uptake in synaptosomes

increased cellular sensitivity to oxidative stress ( J:61249 )

• increased basal and induced lipid peroxidation levels in synaptosomes

decreased cellular glucose uptake ( J:61249 )

• decreased glucose uptake in synaptosomes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:76718 , J:91800 , J:109458 , J:130581

Allelic Composition	Tg(SOD1*G93A)1Gur/?
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(SOD1*G93A)1Gur mutation (4 available)

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

mortality/aging

premature death ( J:107901 )

• mice reach end stage by day 147 +/-2.5 SEM (standard error of measurement)

growth/size/body

decreased body weight ( J:107901 )

• body weights are lower than in wild-type mice and continues to deteriorate after day 115

nervous system

astrocytosis ( J:107901 )

• astrocytosis is evident in the spinal cord

abnormal spinal cord morphology ( J:107901 )

• degeneration of the motor neurons in the cervical and lumbar spinal cord is visible at end stage with astrocytosis and vacuolization

decreased motor neuron number ( J:107901 )

• 50% of motor neurons in the cervical spinal cord and 60% in lumbar spinal cord are degenerated at day 152

behavior/neurological

decreased locomotor activity ( J:107901 )

• mice exhibit decreased locomotor activity compared to wild-type mice after day 115

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