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Phenotypes Associated with This Genotype
Genotype
MGI:3513833
Allelic
Composition
GarsNmf249/Gars+
Genetic
Background
C57BL/6J-GarsNmf249/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
GarsNmf249 mutation (1 available); any Gars mutation (29 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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)

behavior/neurological
• mutant mice develop an unsteady gait by the average age of 3.5 weeks

nervous system
N
• pathological examination revealed no central nervous system abnormality
• immunocytohistology reveals retraction of axons of motor neurons and poor or absent innervation of neuromuscular junctions
• 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)
• 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
• 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
• 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)
• 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

muscle
• 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
• 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

growth/size/body
• mutant mice are smaller than their littermates
• affected mice fail to thrive

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Charcot-Marie-Tooth disease type 2D DOID:0110164 OMIM:601472
J:112221


Contributing Projects:
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
02/23/2021
MGI 6.16
The Jackson Laboratory