Phenotypes associated with this allele

• Allele Symbol: Gars1^C201R
• Allele Name: Cys201Arg
• Allele ID: MGI:3760297
• Summary: 13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gars1^C201R/Gars1^C201R	involves: BALB/cAnN * C3H/HeH	MGI:3849422
hm2	Gars1^C201R/Gars1^C201R	involves: BALB/cAnN * C3H/HeH * C57BL/6J	MGI:3849421
ht3	Gars1^C201R/Gars1^+	involves: BALB/cAnN * C3H/HeH	MGI:3849419
ht4	Gars1^C201R/Gars1^+	involves: BALB/cAnN * C3H/HeH * C57BL/6J	MGI:3849420
ht5	Gars1^Gt(XM256)6Byg/Gars1^C201R	involves: 129P2/OlaHsd * BALB/cAnN * C3H/HeH * C57BL/6J	MGI:5308220
ht6	Gars1^C201R/Gars1^Nmf249	involves: BALB/cAnN * C3H/HeH * C57BL/6J	MGI:5308227
cx7	Gars1^C201R/Gars1^Gt(XM256)6Byg Tg(CAG-GARS)DRwb/0	involves: 129P2/OlaHsd * BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N	MGI:5308219
cx8	Gars1^C201R/Gars1^+ Nrcam^m1J/Nrcam^m1J	involves: BALB/cAnN * C3H/HeH * C57BL/6J	MGI:5882408
cx9	Gars1^C201R/Gars1^+ Tg(Thy1-YFP)16Jrs/?	involves: BALB/cAnN * C3H/HeH * C57BL/6J * CBA	MGI:5752648
cx10	Gars1^C201R/Gars1^Nmf249 Tg(CAG-GARS)DRwb/0	involves: BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N	MGI:5308233
cx11	Gars1^C201R/Gars1^+ Tg(CAG-GARS)DRwb/0	involves: BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N	MGI:5308216
cx12	Gars1^C201R/Gars1^C201R Tg(CAG-GARS)DRwb/0	involves: BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N	MGI:5308222
cx13	Gars1^C201R/Gars1^+ Scn8a^m10J/Scn8a^+	involves: BALB/cAnN * C3H/HeJ * FVB/NJ	MGI:5882425

Genotype
MGI:3849422

hm1

• Allelic Composition: Gars1^C201R/Gars1^C201R
• Genetic Background: involves: BALB/cAnN * C3H/HeH

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

mortality/aging

postnatal lethality, complete penetrance ( J:149830 )

• all mice die by P17

prenatal lethality, incomplete penetrance ( J:149830 )

• half as many mice as expected are born

behavior/neurological

impaired limb coordination ( J:149830 )

abnormal locomotor activation ( J:149830 )

• some mice fail to move to suckle

growth/size/body

decreased body weight ( J:149830 )

• male body weight is decreased 61% compared to in wild-type mice

Genotype
MGI:3849421

hm2

• Allelic Composition: Gars1^C201R/Gars1^C201R
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J

mortality/aging

postnatal lethality, complete penetrance ( J:149830 , J:179811 )

• all mice die by P15 (J:149830)

prenatal lethality, incomplete penetrance ( J:149830 , J:179811 )

• one fifth of expected mice are born (J:149830)

Genotype
MGI:3849419

ht3

• Allelic Composition: Gars1^C201R/Gars1⁺
• Genetic Background: involves: BALB/cAnN * C3H/HeH

behavior/neurological

impaired coordination ( J:149830 )

• mice exhibit impaired coordination on a rotarod compared with wild-type mice

impaired fine motor coordination ( J:149830 )

• in a mouse reach and grasp assay, mice exhibit reduced motor flexibility and decreased fine motor control compared with wild-type mice

decreased grip strength ( J:149830 )

• 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

decreased locomotor activity ( J:149830 )

nervous system

nervous system phenotype ( J:149830 )

N • at E12.5, the peripheral nervous system appears normal

N • at P15 and 17 months, mice exhibit normal brain and spinal cord morphology

abnormal sciatic nerve morphology ( J:149830 )

• at 17 months, the number of large diameter axons in the sciatic nerve is decreased 50% compared to in wild-type mice

Genotype
MGI:3849420

ht4

• Allelic Composition: Gars1^C201R/Gars1⁺
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J

nervous system

nervous system phenotype ( J:179811 )

N • normal axon numbers

abnormal innervation pattern to muscle ( J:149830 )

• reduced in the tibialis anterior and extensor digitorum longus

abnormal sensory neuron morphology ( J:149830 )

• axons within the saphenous nerve exhibit a shift towards smaller diameters compared to in wild-type mice

abnormal neuromuscular synapse morphology ( J:149830 , J:179811 )

• 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)

decreased nerve conduction velocity ( J:149830 , J:179811 )

• 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)

muscle

abnormal tibialis anterior morphology ( J:149830 )

• 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

decreased tibialis anterior weight ( J:149830 )

• in female mice

decreased skeletal muscle fiber number ( J:149830 )

• in the tibialis anterior and the extensor digitorum longus

muscle weakness ( J:149830 )

• 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

behavior/neurological

decreased grip strength ( J:149830 , J:179811 )

• 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)

growth/size/body

decreased body weight ( J:149830 )

• in female mice

limbs/digits/tail

abnormal tibialis anterior morphology ( J:149830 )

• 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

decreased tibialis anterior weight ( J:149830 )

• in female mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 2D		DOID:0110164	OMIM:601472	J:149830 , J:179811

Genotype
MGI:5308220

ht5

• Allelic Composition: Gars1^{Gt(XM256)6Byg}/Gars1^C201R
• Genetic Background: involves: 129P2/OlaHsd * BALB/cAnN * C3H/HeH * C57BL/6J

mortality/aging

prenatal lethality ( J:179811 )

• time not specified

Genotype
MGI:5308227

ht6

• Allelic Composition: Gars1^C201R/Gars1^Nmf249
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J

mortality/aging

mortality/aging ( J:179811 )

N • mutants are viable and born at the expected Mendelian ratios

growth/size/body

decreased body weight ( J:179811 )

• decreased body weight compared to Gars^C201R heterozygotes

nervous system

abnormal axon morphology ( J:179811 )

• the motor branch of the femoral nerve is smaller and axon numbers are reduced

abnormal neuromuscular synapse morphology ( J:179811 )

• 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

Genotype
MGI:5308219

cx7

• Allelic Composition: Gars1^C201R/Gars1^{Gt(XM256)6Byg}; Tg(CAG-GARS)DRwb/0
• Genetic Background: involves: 129P2/OlaHsd * BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N

mortality/aging

mortality/aging ( J:179811 )

N • mutants are born at the expected Mendelian ratios, indicating rescue of the embryonic lethality observed in compound heterozygotes without the transgene

N • while embryonic lethality is rescued with the transgene, severity of neuropathy is similar to single Gars^C201R heterozygotes

growth/size/body

decreased body weight ( J:179811 )

• mutants exhibit lower body weights than single Gars^{Gt(XM256)6Byg} heterozygotes or wild-type mice

nervous system

nervous system phenotype ( J:179811 )

N • mutants exhibit normal numbers of myelinated axons in the motor or sensory branch of the fremoral nerve

abnormal neuromuscular synapse morphology ( J:179811 )

• neuromuscular junctions have regions of immature morphology or denervation, similar to single Gars^C201R heterozygotes

decreased nerve conduction velocity ( J:179811 )

• mutants exhibit reduced nerve conduction velocities, but they are similar to single Gars^C201R heterozygotes

Genotype
MGI:5882408

cx8

• Allelic Composition: Gars1^C201R/Gars1⁺; Nrcam^m1J/Nrcam^m1J
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J

behavior/neurological

tremors ( J:240096 )

impaired coordination ( J:240096 )

• poor motor performance compared with controls, but no progression to paralysis

muscle

muscle hypoplasia ( J:240096 )

• muscles in mice with this compound genotype are smaller than that of either parental mutant alone

nervous system

abnormal innervation pattern to muscle ( J:240096 )

• decreased neuromuscular junction occupancy with an increase in partial innervation as well as some denervation

abnormal axon morphology ( J:240096 )

• 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

abnormal neuromuscular synapse morphology ( J:240096 )

decreased nerve conduction velocity ( J:240096 )

• nerve conductance velocity, assessed in adult sciatic nerve, is reduced further than that in either single parental mutant

Genotype
MGI:5752648

cx9

• Allelic Composition: Gars1^C201R/Gars1⁺; Tg(Thy1-YFP)16Jrs/?
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J * CBA

nervous system

abnormal neuromuscular synapse morphology ( J:229590 )

• 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

abnormal synaptic transmission ( J:229590 )

abnormal PNS synaptic transmission ( J:229590 )

• 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

behavior/neurological

decreased grip strength ( J:229590 )

• 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

Genotype
MGI:5308233

cx10

• Allelic Composition: Gars1^C201R/Gars1^Nmf249; Tg(CAG-GARS)DRwb/0
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N

mortality/aging

mortality/aging ( J:179811 )

N • mutants are viable and born at the expected Mendelian ratios

growth/size/body

decreased body weight ( J:179811 )

• decreased body weight compared to Gars^C201R heterozygotes

nervous system

abnormal axon morphology ( J:179811 )

• the motor branch of the femoral nerve is smaller and axon numbers are reduced

abnormal neuromuscular synapse morphology ( J:179811 )

• 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

Genotype
MGI:5308216

cx11

• Allelic Composition: Gars1^C201R/Gars1⁺; Tg(CAG-GARS)DRwb/0
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N

behavior/neurological

decreased grip strength ( J:179811 )

• mutants exhibit a similar wire hanging deficit as single Gars^C201R heterozygotes

nervous system

decreased nerve conduction velocity ( J:179811 )

• nerve conduction velocities are reduced to a similar extent as in single Gars^C201R heterozygotes

Genotype
MGI:5308222

cx12

• Allelic Composition: Gars1^C201R/Gars1^C201R; Tg(CAG-GARS)DRwb/0
• Genetic Background: involves: BALB/cAnN * C3H/HeH * C57BL/6J * FVB/N

mortality/aging

mortality/aging ( J:179811 )

N • mutants are born at the expected Mendelian ratios, indicating rescue of the prenatal lethality seen in homozygotes

postnatal lethality, complete penetrance ( J:179811 )

• mutants live to a maximum of P20

growth/size/body

decreased body weight ( J:179811 )

nervous system

abnormal axon morphology ( J:179811 )

• mutants exhibit a 50% reduction in axon numbers in the motor branch of the femoral nerve

abnormal neuromuscular synapse morphology ( J:179811 )

• mutants exhibit neuromuscular junction defects, with frank denervation at almost half of the postsynaptic sites

decreased nerve conduction velocity ( J:179811 )

• impaired nerve conduction velocities

Genotype
MGI:5882425

cx13

• Allelic Composition: Gars1^C201R/Gars1⁺; Scn8a^m10J/Scn8a⁺
• Genetic Background: involves: BALB/cAnN * C3H/HeJ * FVB/NJ

nervous system

abnormal motor neuron innervation pattern ( J:240096 )

• neuromuscular junction innervation is decreased compared with either parental mutants, with an increase in both partial innervation and denervation

abnormal neuromuscular synapse morphology ( J:240096 )

decreased nerve conduction velocity ( J:240096 )

• nerve conduction velocity is lower than in either parental mutant