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Allele Symbol Allele Name Allele ID |
Gars1Nmf249 neuroscience mutagenesis facility, 249 MGI:3513831 |
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| Summary |
9 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutant mice die at between 4 and 8 weeks of age
(J:82238)
• most animals die by 6-8 weeks of age, with a few surviving longer than 6 months of age
(J:112221)
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• mutant mice develop an unsteady gait by the average age of 3.5 weeks
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| N |
• pathological examination revealed no central nervous system abnormality
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• immunocytohistology reveals retraction of axons of motor neurons and poor or absent innervation of neuromuscular junctions
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• no large diameter myelinated fibers are observed upon microscopic examination of the sciatic nerve
(J:82238)
• at P7, sciatic nerve axons appear similar in overall size to controls; however, axon diameter distribution studies revealed normal myelin thickness but decreased axon diameter
(J:112221)
• at P35, sciatic nerve axon diameter is decreased further and large-diameter axons are absent; however, internodal distances appear similar to controls
(J:112221)
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• at P36-P37, many partially innervated and some denervated synapses are seen in hindlimb muscles
• innervation similar to controls is seen at P7, suggesting a degenerative process
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• at P7, neuromuscular synapses of hindlimb muscles are fully occupied with motor nerve terminals
• by P36-37, neuromuscular synapses of hindlimb muscles show 31.3 +/- 6.1% partial occupation and 19.9 +/- 5.9% unoccupied with motor nerve terminals, in contrast to controls which remain fully occupied
• this degeneration appears to be length dependent, as less severe pathology at the same stages is seen in the triangularis sterni, an axial muscle of the ribcage
• at P35, examination of sciatic nerve axons reveals an absence of large diameter axons and other degeneration axons as scored by an absence of axoplasm surrounded by a myelin sheath and basal lamina; other axons remained myelinated and did not exhibit any visble pathology
• at P7-P8, the number of myelinated axons of the motor and sensory branches of the femoral nerve is similar to controls; however, by P32-35, there is a significant decrease in both the motor and sensory axon numbers, most notably the large diameter axons
• at 52-61 weeks of age (in rare mice surviving to this age) a modest increase in motor axon loss is femoral nerves is seen with less change seen in sensory axons
• these axonal pathologies appear more severe distally than proximally; at P34, no changes in axon number are seen in the L5 root or in the spinal cord compared to the femoral nerve, which loses 28% of axons
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• sciatic nerve conduction velocity is reduced by 60% in sciatic nerve (10.4 +/- 1.2 m/s vs. 24.4 +/- 5.1 ms in controls)
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• in 8 week old mice, a failure of the production and maintenance of muscle force in gastrocnemius muscle in response to tetanic nerve stimulation is seen
• this failure corresponded to a decreased electromyogram amplitude
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• mice exhibit reduced muscle weight at P36-37 when normalized to body weight; this appears to be due to a smaller muscle fiber size
• no other muscular pathological changes are seen at this age
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• at 52-61 weeks of age (in rare mice surviving to this age) evidence of muscle atrophy and long-term denervation and reinnervation is seen
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• mutant mice are smaller than their littermates
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• affected mice fail to thrive
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Charcot-Marie-Tooth disease type 2D | DOID:0110164 |
OMIM:601472 |
J:112221 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• size of the femoral nerve is reduced
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• 26% reduction in axons in motor nerves
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• partially denervated neuromuscular junctions
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• motor and sensory branches of the femoral nerve have a reduction in myelinated axon numbers
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• nerve conduction is reduced to about 25% of wild-type velocities
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Charcot-Marie-Tooth disease type 2D | DOID:0110164 |
OMIM:601472 |
J:179811 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants are viable and born at the expected Mendelian ratios
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• decreased body weight compared to GarsC201R heterozygotes
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants are viable and born at the expected Mendelian ratios
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• decreased body weight compared to GarsC201R heterozygotes
|
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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, fewer mitochondria at the synaptic terminals, and the average quantal content is significantly lower than normal
• at high magnification, but not evident at low magnification, approximately half of the junctions assesed in the levator auris longus at 2 months of age are found to be only partially innervated, even in the mildly affected mice, and there are more than 3 times as many denervated junctions at 2 months of age as are found in carriers of the C201R allele at 4 months of age
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• at 2 months of age 25% decrease in amplitude of evoked endplate currents, and quantal content in neuromuscular synapses the levator auris longus muscle
• 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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• compared with wild-type controls, heterozygotes have impaired grip strength and this is improved by treatment with physostigmine
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants exhibit a similar decrease in body weight as single GarsNmf249 heterozygotes
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• mutants exhibit a similar reduction in axon numbers in motor and sensory nerves as single GarsNmf249 heterozygotes
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• neuromuscular junctions are disrupted to a similar extent as in GarsNmf249 heterozygotes
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• nerve conduction velocities are similar to single GarsNmf249 heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• slightly more severe than the parental heterozygote
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• decreased neuromuscular junction innervation compared with either parental heterozygotes
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• decreased relative to either parental heterozygote
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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