Analysis Tools
mortality/aging
|
• more than 90% mortality by P50
|
growth/size/body
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• mutants show growth retardation and fail to thrive
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respiratory system
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• intermittent breathing irregularities, including hypo- or hyperventilation and gasping
|
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• breathing rate is variable and lower in restrained mutants than in controls
|
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• mutants exhibit intermittent episodes of apnea and periods during which respiratory frequency is very irregular; number of apnea episodes increases with age
|
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• gasping-like episodes that occur more commonly under stressful conditions, such as when being handled
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• under normoxic conditions, mice at P8-P12 and those older than P30 have normal respiratory frequency, however they have higher tidal volume and minute ventilation
• in response to hypoxia, mutants show an initial augmentation of breathing, followed by a depression
• some mutants exhibit an abnormal response to excess CO2 (hypercapnia), with 6 of 13 mice failing to show the hyperventilation response seen in control mice, while the rest show an exaggerated response
|
nervous system
|
• edematous regions/lesions in the dorsal medulla (in the vestibular nucleus)
• extensive bilateral neuroinflammation in the vestibular nucleus
|
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• edematous regions/lesions in the external plexiform layer of the olfactory bulb
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• edematous regions/lesions in the cerebellar lobes
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• edematous regions/lesions in the deep cerebellar fastigial nucleus
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• neurons with cytoplasmic vacuoles are seen in the brain
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microgliosis
(
J:190475
)
|
• microglial activation is rarely seen in respiratory centers such as the medial parabrachial nucleus, nucleus of the solitary tract or preBotzinger complex, however it is seen in late-stage mutants around serotonergic cell bodies in the medullary raphe
|
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• mutants develop a fatal progressive encephalopathy
• neurons with cytoplasmic vacuoles and aberrant mitochondria containing condensed cristae and microglia engorged with cytoplasmic remnants in the brain
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• mutants exhibit abnormal responses of the Botzinger complex in the ventral medulla under hypoxic conditions; the initial augmentation phase is normal but during depression, the amplitude of fictive gasping is decreased
• intracellular recordings of preBotzinger complex inspiratory neurons show that under control conditions, the depolarization in phase with the network burst is reduced in mutants and the number and frequency of action potentials per burst and firing frequency is lower
• upon transition from control to hypoxic conditions, mutants have a severe reduction of the underlying depolarization when challenged by hypoxia, the number and frequency of action potentials per burst drops dramatically compared to a mild reduction in controls
|
behavior/neurological
cardiovascular system
|
• lower heart rate, especially in late stages of disease
|
homeostasis/metabolism
|
• percentage of oxygen saturation of arterial blood in late-stage mutants is often less than 99% which is not seen in controls
|
immune system
microgliosis
(
J:190475
)
|
• microglial activation is rarely seen in respiratory centers such as the medial parabrachial nucleus, nucleus of the solitary tract or preBotzinger complex, however it is seen in late-stage mutants around serotonergic cell bodies in the medullary raphe
|
integument
muscle
hematopoietic system
microgliosis
(
J:190475
)
|
• microglial activation is rarely seen in respiratory centers such as the medial parabrachial nucleus, nucleus of the solitary tract or preBotzinger complex, however it is seen in late-stage mutants around serotonergic cell bodies in the medullary raphe
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Leigh disease | DOID:3652 |
OMIM:256000 |
J:190475 | |
