Mouse Genome Informatics
cx1
    Gria2tm1Rod/Gria2tm1Rod
Tg(SOD1*G93A)1Gur/0

B6.Cg-Gria2tm1Rod Tg(SOD1*G93A)1Gur
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• shortened lifespan (116.50.6 vs. 137.12.6 days), compare with Tg(SOD1*G93A)1Gur mice

behavior/neurological
• unable to walk on a rotarod
• decreased grip strength in forelimbs
• earlier onset (99.32.1 days vs. 117.31.8 days), compare with Tg(SOD1*G93A)1Gur mice

nervous system
• decreased number of the large neurons in the ventral horn of the lumbar spinal cord
• higher elevations of the intracellular Ca2+ concentration upon AMPA receptor stimulation


Mouse Genome Informatics
cx2
    Gria2tm1Rod/Gria2+
Tg(SOD1*G93A)1Gur/0

B6.Cg-Gria2tm1Rod Tg(SOD1*G93A)1Gur
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• decreased number of the large neurons in the ventral horn of the lumbar spinal cord


Mouse Genome Informatics
cx3
    Tcrbtm1Mom/Tcrb+
Tg(SOD1*G93A)1Gur/0

B6.Cg-Tcrbtm1Mom Tg(SOD1*G93A)1Gur/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• accelerated disease progression
• shorter lifespans than Tg(SOD1*G93A)1Gur and Tg(SOD1*G93A)1Gur, Tcrbtm1Mom heterozygous mice

growth/size
• accelerated weight loss after disease onset compared to Tg(SOD1*G93A)1Gur, Tcrbtm1Mom heterozygous littermates, mainly after day 135

nervous system
• decreased microglia reactivity
• 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, Tcrbtm1Mom heterozygous littermates, mainly after day 135

immune system
• decreased microglia reactivity

hematopoietic system
• decreased microglia reactivity


Mouse Genome Informatics
cx4
    Sirt2tm1.2Jmi/Sirt2tm1.2Jmi
Tg(SOD1*G93A)1Gur/0

involves: 129 * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• as in Tg(SOD1*G93A)1Gur mice

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


Mouse Genome Informatics
cx5
    Als2tm1Deng/Als2tm1Deng
Tg(SOD1*G93A)1Gur/?

involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die of a neurodegenerative disorder by 150 days of age

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


Mouse Genome Informatics
cx6
    Hdac6tm1.1Pmt/Y
Tg(SOD1*G93A)1Gur/0

involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• modest increase in survival compared with Tg(SOD1*G93A)1Gur mice (J:194977)

nervous system
• NMJ innervation of the gastrocnemius muscle is improved compared to in Tg(SOD1*G93A)1Gur mice (J:194977)
• in the ventral horn compared to in Tg(SOD1*G93A)1Gur mice with more pronounced protection of large neurons (J:194977)
• mice exhibit higher compound action potential amplitudes compared with Tg(SOD1*G93A)1Gur mice (J:194977)

behavior/neurological
• same age of onset as in Tg(SOD1*G93A)1Gur mice (J:194977)


Mouse Genome Informatics
cx7
    Slc1a2tm1Kta/Slc1a2+
Tg(SOD1*G93A)1Gur/0

involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• shortened lifespan (137 1.7 vs. 142 1.4 days)

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

nervous system
• 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


Mouse Genome Informatics
cx8
    Cx3cr1tm1Litt/Cx3cr1tm1Litt
Tg(SOD1*G93A)1Gur/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• decreased survival in male mice compared with Tg(SOD1*G93A)1Gur mice

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

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

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


Mouse Genome Informatics
cx9
    Cnr1tm1Map/Cnr1tm1Map
Tg(SOD1*G93A)1Gur/0

involves: 129S1/Sv * 129X1/SvJ * ABH * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• despite similar disease progression, mice exhibit longer life span compared with Tg(SOD1*G93A)1Gur mice


Mouse Genome Informatics
cx10
    Tg(SOD1*G93A)1Gur/0
Vegfatm2Pec/Vegfatm2Pec

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die earlier (107 3 d) than Tg(SOD1*G93A)1Gur mice

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

behavior/neurological
• 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


Mouse Genome Informatics
cx11
    Spi1tm1Ram/Spi1tm1Ram
Tg(SOD1*G93A)1Gur/0

involves: 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• 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
• 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
N
• antibiotic-treated mice exhibit normal growth rates (J:116087)


Mouse Genome Informatics
cx12
    Mmp9tm1Tvu/Mmp9tm1Tvu
Tg(SOD1*G93A)1Gur/0

involves: 129S6/SvEvTac * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice survive 31% longer than Tg(SOD1*G93A)1Gur mice (J:141587)

nervous system
N
• neuron loss observed in Tg(SOD1*G93A)1Gur mice is attenuated (J:141587)

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


Mouse Genome Informatics
cx13
    Tg(SOD1*G93A)1Gur/0
Tg(THY1-SNCA)1Sud/0

involves: 129S6/SvEvTac * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice display neurodegeneration similar to Dnajc5-null mice


Mouse Genome Informatics
cx14
    Faahtm1Crv/Faahtm1Crv
Tg(SOD1*G93A)1Gur/0

involves: 129X1/SvJ * ABH * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• similar to in Tg(SOD1*G93A)1Gur mice

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

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


Mouse Genome Informatics
cx15
    Dctn1tm1Cai/Dctn1+
Tg(SOD1*G93A)1Gur/0

involves: 129X1/SvJ * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice develop paralysis at the same rate as Tg(SOD1*G93A)1Gur mice


Mouse Genome Informatics
cx16
    Baxtm1Sjk/Baxtm1Sjk
Tg(SOD1*G93A)1Gur/0

involves: 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• live 14.6% longer than Tg(SOD1*G93A)1Gur mice

behavior/neurological
• 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
• delayed reactive gliosis (P100 vs P40, compared with Tg(SOD1*G93A)1Gur mice)
• 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 Baxtm1Sjk 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)
• 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
• delayed loss of both distal and proximal myelinated axons
• reduction of myelinated axons in end-stage MG nerve and L4 VR

cellular
• presence of vacuolated mitochondria in the ventral spinal cord at P25
• massive vacuolization in the lumbar ventral spinal cord at P100


Mouse Genome Informatics
cx17
    Dync1h1Cra1/Dync1h1+
Tg(SOD1*G93A)1Gur/?

involves: C3HeB/FeJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice reach end stage by day 167 +/-2.5 SEM (standard error of measurement)

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

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

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


Mouse Genome Informatics
cx18
    Sod2tm1Cje/Sod2+
Tg(SOD1*G93A)1Gur/0

involves: C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• accelerated disease progression
• shorter lifespans than Tg(SOD1*G93A)1Gur mice
• mean decrease in survival is 11 days

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

nervous system
• decreased number of total neurons within the substatia nigra at 110 days of age
• microvesiculation within large ventral horn motor neurons at 90 days of age
• 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 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
• atrophy of the lumbar spinal cord starting at 90 days of age


Mouse Genome Informatics
cx19
    Tg(Myl1-Igf1)1Nros/0
Tg(SOD1*G93A)1Gur/0

involves: C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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 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
• at all stages of disease, including at paralysis stage (123 d)
• altered fiber type composition at 138 d with a shift toward a fast fiber type

nervous system
• decrease in astroglial activation at paralysis stage (123 d) in the spinal cord, compared with Tg(SOD1*G93A)1Gur mice
• motor neuron loss is less severe at 112 and 123 d, compared with Tg(SOD1*G93A)1Gur mice


Mouse Genome Informatics
cx20
    Bbc3tm1Ast/Bbc3tm1Ast
Tg(SOD1*G93A)1Gur/0

involves: C57BL/6 * NZB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• despite the delay in disease progression, lifespan is similar to transgenic mice wild type for Bbc3

nervous system
• 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
• 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
N
• unlike transgenic mice wild type for Bbc3, no decrease in stride length is seen even at 120 days of age (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 begins to significantly decrease at 105 days of age compared to 77 days of age in transgenic mice wild type for Bbc3


Mouse Genome Informatics
cx21
    Tg(SOD1)2Gur/0
Tg(SOD1*G93A)1Gur/0

involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• lifespan is on average 117.7 days

nervous system
• 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
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:109458


Mouse Genome Informatics
cx22
    Tg(Gria2*586N)238.2Rsp/0
Tg(SOD1*G93A)1Gur/0

involves: C57BL/6Ico
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• accelerated disease progression
• decreased survival (1932.93 vs. 208.45.06 days), compared with Tg(SOD1*G93A)1Gur mice

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

behavior/neurological
• lose righting reflex between 12 and 18 weeks
• accelerated onset (87.205.5 vs. 1856.3 days), compared with Tg(SOD1*G93A)1Gur mice
• in all 13 mice


Mouse Genome Informatics
cx23
    Tg(SOD1*G93A)1Gur/0
Wlds/Wlds

involves: C57BL/6J * C57BL/6Ola * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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)


Mouse Genome Informatics
cx24
    Tg(SOD1*G93A)1Gur/0
Wlds/+

involves: C57BL/6J * C57BL/6Ola * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• 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
• delayed denervation at the neuromuscular junction
• more axons and innervated neuromuscular junctions in nerve roots than Tg(SOD1*G93A)1Gur mutants at day 80
• similar levels of ventral root axon loss to that seen in Tg(SOD1*G93A)1Gur mice
• similar levels of dorsal root axon loss to that seen in Tg(SOD1*G93A)1Gur mice

homeostasis/metabolism
• 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


Mouse Genome Informatics
tg25
    Tg(SOD1*G93A)1Gur/0
B6.Cg-Tg(SOD1*G93A)1Gur
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean survivals in male and female mice are 153 2 and 161 2 days respectively

growth/size
• decreased body weight starting at P65

behavior/neurological
• tremor onset occurred significantly sooner in male (912 days) compared to female (1002 days)
• deficits in rotarod test
• deficits in paw grip endurance test (PaGE)
• delayed chronic deficits in female compared to male
• 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
• 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
• 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
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:155140


Mouse Genome Informatics
tg26
    Tg(SOD1*G93A)1Gur/0
B6.Cg-Tg(SOD1*G93A)1Gur/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• disease onset at 1111.8 days (d) (J:95812)
• die within 100.6 d of clinical disease onset (J:95812)
• maximal life span of 145 d (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 (143.67.5 days) in contrast to B6SJL/J background (130.211.2 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)

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

muscle
• at 112 d and 123 d compared with wild-type mice
• severe muscle atrophy at 123 d
• altered fiber type composition at 80 d with a shift toward a fast fiber type

nervous system
• 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

immune system
• diminished follicular area by 67% with a greater number (41%) of follicles at end stage
• reduced spleen weight (59%) at 22 weeks of age
• reduced viable spleen cell numbers (70%) at 22 weeks of age
• progressively diminished proliferative capacity of T cells with age

hematopoietic system
• diminished follicular area by 67% with a greater number (41%) of follicles at end stage
• reduced spleen weight (59%) at 22 weeks of age
• reduced viable spleen cell numbers (70%) at 22 weeks of age
• progressively diminished proliferative capacity of T cells with age


Mouse Genome Informatics
tg27
    Tg(SOD1*G93A)1Gur/0
B6SJL-Tg(SOD1*G93A)1Gur
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• decreased density of ChAT-boutons at 16 weeks of age
• 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
• decreased spine density on basal dendrite segments of branch order four
• 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
• 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 number of motoneurons at 14 weeks of age
• the number of motoneurons is reduced further at 16 weeks of age
• 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
• 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 number of Renshaw cells at 12 and 14 weeks of age
• decreased density of ChAT-boutons at 16 weeks of age
• swollen, degenerating axons with segmental enlargements in the ventral horn neuropil at 10 weeks of age
• swollen, degenerating axons with segmental enlargements in the white matter at 10 weeks of age

cellular
• 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
• 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
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:144199


Mouse Genome Informatics
tg28
    Tg(SOD1*G93A)1Gur/0
B6SJL-Tg(SOD1*G93A)1Gur/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

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

mortality/aging
• 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
• progressive decrease in lick rhythm over time beginning at approximately 102 days of age
• slightly increased anxiety-related behavior
• reduced mean time spent in the center of the open field from 4 months on
• hind limb tremors at 14 weeks of age (J:138237)
• mild hindlimb tremor at 90 days of age (J:146652)
• lower performance rate (<90%) in rotarod test from 71 days of age
• failed rotarod test after 113 days of age
• 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)
• 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
• 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
• 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)
• 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)
• degenerating somata in the brain at 4 months of age
• 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)
• degeneration lesions in the retrorubral field
• degeneration lesions in the deep layers of the colliculi superior
• heavily filled with Gallyas+, coiled and ballooned axonal and dendritic profiles in the oculomotor ,the trochlear nucleus at 4 months of age
• degeneration lesions in the substantia nigra
• degeneration lesions in the neuropil of the ventral tegmental field
• spongio-form degenerative changes in the red nucleus
• degenerative changes in the globus pallidus at 5 months of age
• degenerative changes in the hypothalamic nuclei at 5 months of age
• degeneration lesions in the nucleus anterior thalami
• 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
• 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)
• swollen, progressive degeneration of astrocytes in the brainstem, cervical and lumbar spinal cord
• characterized by mitochondrial damage, cellular edema and cell rupture
• appear simultaneously to the degenerative changes and increase substantially with time
• 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)
• 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
• 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)
• increased mitochondria in cell bodies of motoneurons (J:129976)
• decreased mitochondria in axonal mitochondria (J:129976)
• increased intermitochondrial distance by 30-50% in axons (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)
• 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
• 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)
• 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
• 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
• increased number of retrograde mitochondria by around 80% after fast axonal transport (FAT)
• decreased fraction of anterograde mitochondria

cellular
• 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)
• 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
• reduced numbers of short, 'broken' cristae in the terminals at 10 weeks of age
• lower aspect ratio showing rounding up mitochondria
• enlarged mitochondria with vacuoles, invading the sarcomeric A band
• swollen mitochondria
• 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)
• loss of mitochondrial inner membrane potential in fiber segments near the neuromuscular junction starting at the age of 37 days
• reduced mitochondrial electron transport activity

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

muscle
• enlarged mitochondria with vacuoles, invading the sarcomeric A band
• greater osmotic stress-induced Ca2+ release activity in fiber segments with depolarized mitochondria
• 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)
• 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
• reduced WBC numbers
• normal neutrophil levels
• decreased number of circulating monocytes
• increased basophil number compared with Tg(SOD1)2Gur mice
• a number of lymphocytes spontaneously form rosettes with autologous erythrocytes in two thirds of the mice
• decreased number of circulating eosinophils
• lower lymphocyte density
• 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)
• 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)
• diminished follicular architecture with a greater number of follicles at end stage
• reduced spleen size at end stage (20-22 weeks of age)
• reduced spleen weight (45%) at 19 weeks of age
• decreased levels of CD45RA+ (naive) T cells
• increased levels of CD45RO+ (memory) T cells
• increased annexin-V associated apoptosis and necrosis of lymphocytes at pre-symptomatic stage (14 weeks of age)
• 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
• no weight gain beginning at approximately 108 days of age

cardiovascular system
• 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
• 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
• reduced WBC numbers
• normal neutrophil levels
• decreased number of circulating monocytes
• increased basophil number compared with Tg(SOD1)2Gur mice
• a number of lymphocytes spontaneously form rosettes with autologous erythrocytes in two thirds of the mice
• decreased number of circulating eosinophils
• lower lymphocyte density
• increased granularity starting at day 100 (J:143173)
• increased cell size starting at day 100 (J:143173)
• large vacuoles in microglial cell cytoplasm in the cervical and lumbar spinal cord (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)
• diminished follicular architecture with a greater number of follicles at end stage
• reduced spleen size at end stage (20-22 weeks of age)
• reduced spleen weight (45%) at 19 weeks of age
• increased levels of CD45RO+ (memory) T cells
• decreased levels of CD45RA+ (naive) T cells
• increased annexin-V associated apoptosis and necrosis of lymphocytes at pre-symptomatic stage (14 weeks of age)

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:133155 , J:143173 , J:146652


Mouse Genome Informatics
tg29
    Tg(SOD1*G93A)1Gur/0
involves: ABH * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: mice on a background containing ABH exhibit shorter life span than mice on a mixed C57BL/6 and SJL background


Mouse Genome Informatics
tg30
    Tg(SOD1*G93A)1Gur/0
involves: C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• decreased number of total neurons within the substatia nigra at 110 days of age
• decreased number of total neurons within the ventral horns of the lumbar cord at 110 days of age
• decreased number of total neurons within the ventral horns of the lumbar cord at 110 days of age


Mouse Genome Informatics
tg31
    Tg(SOD1*G93A)1Gur/0
involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

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

mortality/aging
• die after 124 4 days (J:84843)
• die within 7-10 days after paralysis (J:109423)
• lifespan is on average 127.4 days (J:111498)
• 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
• lower body mass
• body weight begins to significantly decrease at 77 days of age

nervous system
• 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)
• 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)
• 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
• mutant SOD1-positive inclusions in the ventral horn starting at P30
• the number of motoneurons with aggregates decreased dramatically over time
• motoneuron loss beyond 3 months of age
• 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)
• mutants develop amyotrophic lateral sclerosis-like disease, with onset of disease on average at 103.2 days
• increased infarct volume at 24 hours after transient focal cerebral ischemia
• increased expression of unfolded protein response target genes by 50 days of age in motor neurons
• abnormal corticostriatal synaptic plasticity between postnatal days 100 and 110
• intracellular recordings of single excitatory postsynaptic potentials from striatal medium spiny neurons showing an LTP, instead of an LTD
• 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
• 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
• trend towards less susceptible to paired-pulse depression

behavior/neurological
• less conditioned responses
• less increased performance as training proceeds
• normal minimal foot-shock intensity eliciting vocalization
• 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
• unable to stay for 2 min on the rotarod beyond 118 4 days of age
• steady decline in paw grip endurance beginning at 77 days of age
• locomotor activity decreases more rapidly across 5 sessions
• impairment in walking patterns with reduced stride length beginning at 90 days of age
• beginning at 90 days of age
• 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)
• develop a progressive worsening paresis involving primarily the hind limbs with atrophy of the skeletal musculature

muscle
• develop atrophy of skeletal musculature
• 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
• severe muscle weakness beyond 3 months of age (J:84843)
• hindlimb weakness from 4 months of age (J:109423)

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

homeostasis/metabolism
• plasma leptin levels are diminished
• exhibit increased energy expenditure at rest
• increased spinal cord iNOS activity at 117 and 165 days of age
• decreased spinal cord nNOS activity at 165 days of age
• exhibit higher rates of total oxygen consumption
• increased infarct volume at 24 hours after transient focal cerebral ischemia

cellular
• decreased glutamate uptake in synaptosomes
• increased basal and induced lipid peroxidation levels in synaptosomes
• decreased glucose uptake in synaptosomes

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:76718 , J:91800 , J:109458 , J:130581


Mouse Genome Informatics
tg32
    Tg(SOD1*G93A)1Gur/0
involves: C57BL/6Ico
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• decreased survival (208.45.06 vs. >350 days), compared with wild-type mice

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

behavior/neurological
• onset at 1856.3 days
• in only 3 of 11 mice


Mouse Genome Informatics
tg33
    Tg(SOD1*G93A)1Gur/0
involves: C57BL/6J * C57BL/Ola * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice reach end stage by day 131.13.7

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


Mouse Genome Informatics
tg34
    Tg(SOD1*G93A)1Gur/?
involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice reach end stage by day 147 +/-2.5 SEM (standard error of measurement)

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

nervous system
• astrocytosis is evident in the spinal cord
• degeneration of the motor neurons in the cervical and lumbar spinal cord is visible at end stage with astrocytosis and vacuolization
• 50% of motor neurons in the cervical spinal cord and 60% in lumbar spinal cord are degenerated at day 152

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