Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menkes gene (Mc1 or MNK, encoding putative copper-transporting ATPase) expression was investigated and compared in normal and macular mutant mouse brain. Northern blot analysis showed a distinct 8.3-kb transcript and no obvious difference in size or extent in normal mice and macular mutants on postnatal days 0, 4, 7, 10 or 13. In situ hybridization revealed that certain specific populations of cells in the brain express Menkes mRNA, and that their localization in normal and mutant mice did not differ and was conserved on days 4, 10 and 13. The most intense hybridization signals were observed in the hippocampal CA1 region and dentate gyrus, the olfactory bulb nuclei, the cerebellar granular cell layer, the choroid plexus and the ependyma, with less intense signals in the hippocampal CA3 region and cerebellar Purkinje cells. In addition, necrotic neuronal cell death was predominantly observed in the CA3 region and the Purkinje cells of macular mice after postnatal day 10. The finding that the regions that had lower expression level of Menkes mRNA corresponded to those showing neuronal necrosis suggests that the Menkes gene may be responsible for the neuronal degeneration in some specific portions of the brain and clinical manifestations in this mutant.
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PMID:Localization of Menkes gene expression in the mouse brain; its association with neurological manifestations in Menkes model mice. 874 Feb 28

We investigated the role of amidated neuropeptides, and specifically pituitary adenylyl cyclase-activating polypeptide (PACAP), in olfactory neurogenesis and olfactory receptor neuronal survival. Using both immunohistochemistry and in situ hybridization, we find that both peptidylglycine alpha-amidating monooxygenase (PAM), the enzyme responsible for amidation and therefore activation of all amidated neuropeptides, and amidated PACAP are expressed in developing and adult olfactory epithelium. Amidated PACAP is highly expressed in proliferative basal cells and in immature olfactory neurons. The PACAP-specific receptor PAC(1) receptor is also expressed in this population, establishing that these cells can be PACAP responsive. Experiments were conducted to determine whether amidated neuropeptides, such as PACAP38, might function in olfactory neurogenesis and neuronal survival. Addition of PACAP38 to olfactory cultures increased the number of neurons to >250% of control and stimulated neuronal proliferation and survival. In primary olfactory cultures, pharmacologically decreased PAM activity, as well as neutralization of PACAP38, caused neuron-specific loss that was reversed by PACAP38. Mottled (Brindled) mice, which lack a functional ATP7A copper transporter and serve as a model for Menkes disease, provided an in vivo partial loss-of-function PAM knock-out. These mice had decreased amidated PACAP production and concomitant decreased numbers of olfactory receptor neurons. These data establish amidated peptides and specifically PACAP as having important roles in proliferation in the olfactory system and suggest that a similar function exists in vivo.
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PMID:Pituitary adenylyl cyclase-activating peptides and alpha-amidation in olfactory neurogenesis and neuronal survival in vitro. 1142 90

Menkes disease (MD) is a neurodegenerative disorder caused by mutation of the copper transporter ATP7A. While several enzymes expressed in mature neurons require copper, MD neurodegenerative changes cannot be explained by known requirements for ATP7A in neuronal development. To investigate additional roles for ATP7A during development, we characterized its pattern of expression using the olfactory system as a neurodevelopmental model. ATP7A expression in neurons was developmentally regulated rather than constitutively. Initially expressed in the cell bodies of developing neurons, ATP7A protein later shifted to extending axons, peaking prior to synaptogenesis. Similarly, after injury-stimulated neurogenesis, ATP7A expression increased in neurons and axons preceding synaptogenesis. Interestingly, copper-transport-deficient ATP7A still exhibits axonal localization. These results support a role for ATP7A in axon extension, which may contribute to the severe neurodegeneration characteristic of MD.
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PMID:The developmentally regulated expression of Menkes protein ATP7A suggests a role in axon extension and synaptogenesis. 1613 91

Menkes disease (MD) is a neurodegenerative disorder caused by mutations in the copper transporter, ATP7A, a P-type ATPase. We previously used the olfactory system to demonstrate that ATP7A expression is developmentally, not constitutive, regulated, peaking during synaptogenesis when it is highly expressed in extending axons in a copper-independent manner. Although not known to be associated with axonal functions, we explored the possibility that the inability of mutant ATP7A to support axon outgrowth contributes to the neurodegeneration seen in MD. In vivo analysis of the olfactory system in mottled brindled (Atp7aMobr) mice, a rodent model for MD, demonstrates that ATP7A deficiency affects olfactory sensory neuron (OSN) maturation. Disrupted OSN axonal projections and mitral/tufted cell dendritic growth lead to altered synapse integrity and glomerular disorganization in the olfactory bulbs of Atp7aMobr mice. Our data indicate that the neuronal abnormalities observed in MD are a result of specific age-dependent developmental defects. This study demonstrates a role for ATP7A and/or copper in axon outgrowth and synaptogenesis, and will further help identify the cause of the neuropathology that characterizes MD.
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PMID:ATP7A (Menkes protein) functions in axonal targeting and synaptogenesis. 1721 39