Analysis Tools
mortality/aging
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• perinatal lethality, with death before P1
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respiratory system
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• harvest just prior to birth at E18.5, shows that only 33% of mutants take one spontaneous breath and no mutants show further spontaneous respiratory effort, become cyanotic, and all die within minutes of delivery
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nervous system
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• loss of TH neurons in the mesencephalic trigeminal nucleus nuclei
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• the locus coeruleus is abnormal and fails to express tyrosine hydroxylase (TH), indicating absence of TH neurons; sparse and small neuronal cell bodies are seen suggesting cellular loss/attrition of these neurons
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• abnormalities in noradrenergic circuits, including caudal hindbrain nuclei A1/C2 and the forebrain projections of locus coeruleus to hypothalamus
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• loss of TH neurons in the locus coereleus, the dorsal motor nucleus of the vagus, and mesencephalic trigeminal nucleus nuclei
• however, neuronal precursors of the dorsal motor nucleus of the vagus (DMNV) are detectable at E13.5 indicating that progenitor specification occurs
• however, serotonergic neurons that express tryptophan hydroxylase and 5HT appear normal and no gross abnormalities in forebrain are seen
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• abnormal formation of the seventh cranial nerve (CNVII, facial nucleus) in the embryonic brainstem is due to failure of precursor migration
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• loss of TH neurons in the dorsal motor nucleus of the vagus
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• electrophysiological recordings from E18.5 ex vivo brain stem shows depression of endogenous respiratory motor root output under baseline conditions and in response to the excitatory neuropeptide, substance P
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homeostasis/metabolism
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congenital central hypoventilation syndrome | DOID:0060731 |
OMIM:209880 |
J:331513 | |
