Analysis Tools
mortality/aging
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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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behavior/neurological
abnormal gait
(
J:82238
)
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• mutant mice develop an unsteady gait by the average age of 3.5 weeks
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nervous system
| 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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muscle
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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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growth/size/body
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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 | |
