Analysis Tools
mortality/aging
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• mice have an average lifespan of approximately 16-17 days, ranging from 12 to 22 days
• mice intracerebroventricular (ICV) injected with a high dose of adeno-associated virus expressing human IGHMBP2 (ssAAV9-IGHMBP2) at P2 achieve survival over 100 days
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growth/size/body
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• by P7, mice are smaller in size
• however, mice are indistinguishable from wild-type mice at birth
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• by P7, mice weigh less than wild-type mice and by P16, mice show severely reduced weight
• ICV injected mice with a high dose of ssAAV9-IGHMBP2 at P2 gain over 10 g during their lifespan
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behavior/neurological
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• mice take longer to right their positions at P8 and this does not improve throughout the remainder of life
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integument
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• by P16, mice show reduced coat quality
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muscle
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• gastrocnemius and diaphragm muscle shows a reduction in mean muscle fiber area and perimeter
• ICV injection of the high dose adenovirus expressing human IGHMBP2 slightly improves muscle fiber size in gastrocnemius and improves muscle fiber size in the diaphragm
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• mice exhibit hindlimb muscle atrophy; hindlimb splay defects become apparent as early as P7 and by P16, mice show severe contractures with little to no mobility in the hindlimbs and reduced motility in the forelimbs
• ICV injected mice with a high dose of ssAAV9-IGHMBP2 at P2 show improvements in motor function
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nervous system
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• the number of motor neurons in the L3-L5 lumbar spinal cord region is reduced at P15 area and perimeter of motor neurons is reduced, indicating degeneration
• ICV injected mice with a high dose of ssAAV9-IGHMBP2 show reduced neuron degeneration
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• mice exhibit decreased number of fully innervated end plates at P7 in the gastrocnemius muscle, extensor digitorum longus, tibialis anterior muscle, plantaris muscle, and soleus muscle
• at P15, 60% of NMJs are denervated in the gastrocnemius, indicating progressive denervation
• however, the transverse abdominis and rectus abdominis abdominal wall muscles and diaphragm muscles do not show denervation
• ICV injection of the high dose adenovirus expressing human IGHMBP2 prevents denervation
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respiratory system
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• under normoxia conditions, mice show higher tidal volume that is increased further under hypercapnia + hypoxia conditions
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• mice challenged with hypercapnia + hypoxia, do not respond by increasing ventilation and mean inspiratory flow as seen in wild-type mice
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• under normoxia conditions, mice have decreased respiratory frequency
• respiratory frequency decreases further when challenged with hypercapnia + hypoxia conditions instead of increasing as in wild-type mice
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• number of apneas is increased under normoxia conditions but not during hypercapnia + hypoxia
• ICV injection of the high dose of ssAAV9-IGHMBP2 improves respiratory frequency, the number of apneas and erratic breathing nearly to wild-type
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• mice challenged with hypercapnia + hypoxia, do not respond by increasing ventilation as in wild-type mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autosomal recessive distal hereditary motor neuronopathy 1 | DOID:0111064 |
OMIM:604320 |
J:326540 | |
