Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
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mortality/aging
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• half as many mice as expected are born
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behavior/neurological
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• some mice fail to move to suckle
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growth/size/body
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• male body weight is decreased 61% compared to in wild-type mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
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mortality/aging
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• all mice die by P15
(J:149830)
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• one fifth of expected mice are born
(J:149830)
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Allelic
Composition |
Gars1C201R/Gars1+
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Genetic
Background |
involves: BALB/cAnN * C3H/HeH |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
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behavior/neurological
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• mice exhibit impaired coordination on a rotarod compared with wild-type mice
• in a mouse reach and grasp assay, mice exhibit reduced motor flexibility and decreased fine motor control compared with wild-type mice
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• Background Sensitivity: male mouse grip strength is reduced 40% compared to that of wild-type mice on mixed BALB/cAnN and C3H/HeH background whereas grip strength is reduced 57% on a mixed BALB/cAnN, C3H/HeH, and C57BL/6 background
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nervous system
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N |
• at E12.5, the peripheral nervous system appears normal
• at P15 and 17 months, mice exhibit normal brain and spinal cord morphology
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• at 17 months, the number of large diameter axons in the sciatic nerve is decreased 50% compared to in wild-type mice
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Allelic
Composition |
Gars1C201R/Gars1+
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Genetic
Background |
involves: BALB/cAnN * C3H/HeH * C57BL/6J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
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nervous system
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• reduced in the tibialis anterior and extensor digitorum longus
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• axons within the saphenous nerve exhibit a shift towards smaller diameters compared to in wild-type mice
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• neuromuscular junctions (NMJs) in the extensor digitorum longus are smaller with much less complex geometry compared to in wild-type mice
(J:149830)
• the tibialis anterior NMJs exhibit regions of partial innervation and portions of the terminal arbor appear atrophied unlike in wild-type mice
(J:149830)
• neuromuscular junctions have regions of immature morphology or denervation
(J:179811)
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• sensory nerve compound action potentials exhibit reduced conduction velocity and amplitude compared to in wild-type mice
(J:149830)
• nerve conduction velocities are reduced to about 55% of wild-type levels
(J:179811)
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muscle
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• the tibialis anterior exhibits increased oxidative capacity, loss of muscle fibers, and increased cross-sectional fiber area consistent with denervation atrophy and compensatory hypertrophy unlike in wild-type mice
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• in the tibialis anterior and the extensor digitorum longus
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• the maximum twitch and tetanic forces of the tibialis anterior are less than those of wild-type muscle
• however, the force output of the extensor digitorum longus is normal
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behavior/neurological
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• Background Sensitivity: male mouse grip strength is reduced 57% compared to that of wild-type mice on mixed BALB/cAnN, C3H/HeH, and C57BL/6 background whereas grip strength is reduced 40% on a mixed BALB/cAnN and C3H/HeH background
(J:149830)
• mutants exhibit wire hanging deficits, unable to hang for the entire task time
(J:179811)
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growth/size/body
limbs/digits/tail
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• the tibialis anterior exhibits increased oxidative capacity, loss of muscle fibers, and increased cross-sectional fiber area consistent with denervation atrophy and compensatory hypertrophy unlike in wild-type mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Gars1Gt(XM256)6Byg mutation
(0 available);
any
Gars1 mutation
(42 available)
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mortality/aging
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N |
• mutants are viable and born at the expected Mendelian ratios
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growth/size/body
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• decreased body weight compared to GarsC201R heterozygotes
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nervous system
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• the motor branch of the femoral nerve is smaller and axon numbers are reduced
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• mutants exhibit more severe neuromuscular junction defects than either allele as a heterozygote, with a majority of neuromuscular junctions partially or fully denervated and very few that are fully innervated
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Gars1Gt(XM256)6Byg mutation
(0 available);
any
Gars1 mutation
(42 available)
Tg(CAG-GARS)DRwb mutation
(0 available)
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mortality/aging
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N |
• mutants are born at the expected Mendelian ratios, indicating rescue of the embryonic lethality observed in compound heterozygotes without the transgene
• while embryonic lethality is rescued with the transgene, severity of neuropathy is similar to single GarsC201R heterozygotes
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growth/size/body
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• mutants exhibit lower body weights than single GarsGt(XM256)6Byg heterozygotes or wild-type mice
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nervous system
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N |
• mutants exhibit normal numbers of myelinated axons in the motor or sensory branch of the fremoral nerve
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• neuromuscular junctions have regions of immature morphology or denervation, similar to single GarsC201R heterozygotes
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• mutants exhibit reduced nerve conduction velocities, but they are similar to single GarsC201R heterozygotes
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Nrcamm1J mutation
(0 available);
any
Nrcam mutation
(87 available)
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behavior/neurological
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• poor motor performance compared with controls, but no progression to paralysis
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muscle
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• muscles in mice with this compound genotype are smaller than that of either parental mutant alone
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nervous system
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• decreased neuromuscular junction occupancy with an increase in partial innervation as well as some denervation
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• reduced axon size in the motor branch of the femoral nerve, similar to that of glycyl-tRNA synthetase mutant mice wildtype for neuronal cell adhesion molecular
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• nerve conductance velocity, assessed in adult sciatic nerve, is reduced further than that in either single parental mutant
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Tg(Thy1-YFP)16Jrs mutation
(1 available)
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nervous system
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• at high magnification, but not evident at low magnification, approximately 5% of the neuromuscular junctions assesed in the levator auris longus at 4 months of age are found to be only partially innervated, far fewer than in Nmf249 heterozygotes
• nearly all terminals assessed in the levator auris longus show more diffuse postsynaptic staining, less distinct gutters, thinner axons and presynaptic nerves, synapses that are smaller than in wild-type controls, the average quantal content is significantly lower than normal, and the quantal content and mean evoked endplate currents are lower still at 4 months compared with 2 months
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• at 2 months of age 25% decrease in amplitude of evoked endplate currents, and quantal content in neuromuscular synapses of the levator auris longus muscle, and treatment with 3,4-DAP or physostigmine increases the in vivo evoked endplate currents at 4 months of age
• at 2 months of age the frequency of spontaneous release is consistently lower than normal although the quantal amplitude at synapses is normal, and no differences are found in the miniature endplate current amplitude
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behavior/neurological
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• compared with wild-type controls, heterozygotes have impaired grip strength and this is improved by treatment with physostigmine, but made worse by treatment with 3,4-DAP
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Gars1Nmf249 mutation
(1 available);
any
Gars1 mutation
(42 available)
Tg(CAG-GARS)DRwb mutation
(0 available)
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mortality/aging
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N |
• mutants are viable and born at the expected Mendelian ratios
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growth/size/body
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• decreased body weight compared to GarsC201R heterozygotes
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nervous system
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• the motor branch of the femoral nerve is smaller and axon numbers are reduced
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• mutants exhibit more severe neuromuscular junction defects than either allele as a heterozygote, with a majority of NMJs partially or fully denervated and very few that are fully innervated
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Tg(CAG-GARS)DRwb mutation
(0 available)
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behavior/neurological
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• mutants exhibit a similar wire hanging deficit as single GarsC201R heterozygotes
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nervous system
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• nerve conduction velocities are reduced to a similar extent as in single GarsC201R heterozygotes
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Tg(CAG-GARS)DRwb mutation
(0 available)
|
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mortality/aging
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N |
• mutants are born at the expected Mendelian ratios, indicating rescue of the prenatal lethality seen in homozygotes
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• mutants live to a maximum of P20
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growth/size/body
nervous system
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• mutants exhibit a 50% reduction in axon numbers in the motor branch of the femoral nerve
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• mutants exhibit neuromuscular junction defects, with frank denervation at almost half of the postsynaptic sites
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• impaired nerve conduction velocities
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Allelic
Composition |
Gars1C201R/Gars1+
Scn8am10J/Scn8a+
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Genetic
Background |
involves: BALB/cAnN * C3H/HeJ * FVB/NJ |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gars1C201R mutation
(2 available);
any
Gars1 mutation
(42 available)
Scn8am10J mutation
(0 available);
any
Scn8a mutation
(99 available)
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nervous system
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• neuromuscular junction innervation is decreased compared with either parental mutants, with an increase in both partial innervation and denervation
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• nerve conduction velocity is lower than in either parental mutant
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Analysis Tools