Analysis Tools
mortality/aging
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• 60% die before or around birth while the remaining 40% survive more than 23 months
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• 60% die before or around birth while the remaining 40% survive more than 23 months
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growth/size/body
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• surviving mutants are about 25% smaller at birth
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• surviving mutants gain about 45% less weight than wild-type
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behavior/neurological
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• mutants develop coarse fur indicative of impaired grooming
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• mutants have difficulty turning over when placed on their backs at 5 months of age and can hardly turn over at all by 15 months of age
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limb grasping
(
J:69797
)
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• when lifted by the tail, mutants reflexively contract their limbs to the trunk and remain immobile
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• in the grid test, mutants fall off the grid much quicker than wild-type
• mutants perform worse in the rotating axle test, falling off much quicker than wild-type
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• mutants have difficulties in grabbing a horizontal thread with their hindlimbs and hang immobile, while wild-type immediately grab the thread
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abnormal gait
(
J:69797
)
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• mutants slap their paws while walking and have a waddling gait
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• mutants are less active at night and for much shorter periods than wild-type
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• severely paralysis after ischemic insult by clamping the aortic arch, left subclavian artery and internal mammary artery for only 8 min
• no recovery neurologically
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• older males are sexually inactive, possibly due to motor dysfunction
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muscle
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• progressive skeletal muscle fiber atrophy after 4 months of age; atrophy is specific for extrafusal muscle fibers and does not affect muscle spindles or cardiac muscle fibers
• however show no signs of fiber necrosis, sarcomere lysis or sarcolemma disruption, fatty infiltration, fibrosis or dystrophic calcification
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• latencies of compound muscle action potentials are slightly increased
• the ankle dorsal flexor muscles of old mice generate only 65% of the maximal force upon tetanic stimulation
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• mutants become progressively less mobile and show signs of severe muscle weakness and limb paresis
• muscle weakness is not due to impaired oxygenation or reduced levels of hemoglobin
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nervous system
astrocytosis
(
J:69797
)
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• prominent reactive astrocytosis in the ventral horn of the spinal cord is seen beyond 7 months of age
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• focal spheroid axon swellings often occur in several cranial motor nerves and in the ventral horns of the spinal cords beyond 7 months of age
• mutants show features of Wallerian degeneration, including shrunken vacuolated axoplasm, disorganized neurofilaments, few abnormal mitochondria, endoneural fibrosis, and infiltration of macrophages
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• aberrant neurofilament accumulation is seen in the motor, but not sensory, nuclei or roots of several cranial nerves in mutants older than 7 months of age
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• phrenic nerves progressively lose their large myelinated Agamma motor axons, which innervate the extrafusal muscle fibers
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• sciatic nerves progressively lose their large myelinated Agamma motor axons, which innervate the extrafusal muscle fibers
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• phosphorylated neurofilament inclusions are seen in the ventral horns of older mutants
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• neurodegeneration is due to reduced neural vascular perfusion
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• surviving mutants appear healthy until 5 months of age, when they develop progressive motor neuron degeneration of lower motor neurons
• motor neuron degeneration occurs especially in the ventral horn of the spinal cord (30% loss at 17 months) and the motor nuclei in the brain stem
• loss of motor axons in peripheral nerves
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• sciatic and phrenic nerves progressively lose their large myelinated Agamma motor axons, which innervate the extrafusal muscle fiber
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reproductive system
skeleton
cardiovascular system
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• in skeletal muscle, capillary lumen sizes are smaller
• however, capillary-to-muscle ratios, fluoroangiography, and microvascular partial oxygen pressure were normal, indicating that motor neuron degeneration is not secondary to muscle ischemia
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• laser Doppler measurements show that baseline neural blood flow is lower than in wild-type, even though the neural vascular flow similarly increases by about 40% in response to hypercapnia, indicating a deficit in neural vascular perfusion
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integument
coarse hair
(
J:69797
)
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• mutants develop coarse fur indicative of impaired grooming
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respiratory system
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• a small fraction of mutants that die at birth exhibit lung prematurity
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atelectasis
(
J:77480
)
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• in a small fraction of mutants, lung aeration (percentage of total surface filled with air) fails to increase after birth
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• in a small fraction of mutants, a significantly increased alveolar septal thickness is noted at birth
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| amyotrophic lateral sclerosis type 1 | DOID:0060193 |
OMIM:105400 |
J:69797 | |
