Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease.

Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease. Research Abstract Details 

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Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease. Abstract Text:

Mark J Niciu,Xin-Ming Ma, El Meskini,Joel S Pachter,Richard E Mains,Betty A Eipper,

Mutations in the copper-transporter ATP7A lead to severe neurodegeneration in the mottled brindled hemizygous male (MoBr/y) mouse and human patients with Menkes disease. Our earlier studies demonstrated cell-type- and -stage-specific changes in ATP7A protein expression during postnatal neurodevelopment. Here we examined copper and cuproenzyme levels in MoBr/y mice to search for compensatory responses. While all MoBr/y neocortical subcellular fractions had decreased copper levels, the greatest decrease (8-fold) was observed in cytosol. Immunostaining for ATP7A revealed decreased levels in MoBr/y hippocampal pyramidal and cerebellar Purkinje neurons. In contrast, an upregulation of ATP7A protein occurred in MoBr/y endothelial cells, perhaps to compensate for a lack of copper in the neuropil. MoBr/y astrocytes and microglia increased their physical association with the blood-brain barrier. No alterations in ATP7A levels were observed in ependymal cells, arguing for specificity in the alteration observed at the blood-brain barrier. The decreased expression of ATP7A protein in MoBr/y Purkinje cells was associated with impaired synaptogenesis and dramatic cytoskeletal dysfunction. Immunoblotting failed to reveal any compensatory increase in levels of ATP7B. While total levels of several cuproenzymes (peptide-amidating monooxygenase, SOD1, and SOD3) were unaltered in the MoBr/y brain, levels of amidated cholecystokinin (CCK8) and amidated pituitary adenylate cyclase-activating polypeptide (PACAP38) were reduced in a tissue-specific fashion. The compensatory changes observed in the neurovascular unit provide insight into the success of copper injections within a defined neurodevelopmental period.

Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease. Publishing Authors By Initials

MJ Niciu,XM Ma,R El Meskini,JS Pachter,RE Mains,BA Eipper,

For similar nervous system: neurons research abstracts see: nervous system: neurons research

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Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Neurobiology of disease

VOLUME: 27

Page Numbers: 278-91

Journal Abbreviation: Neurobiol. Dis.

ISSN: 0969-9961

DAY: 23

MONTH: 05

YEAR: 2007

Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease. Information

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LANGUAGE: eng

NlmUniqueID: 9500169

Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease. Keywords Mesh Terms:

KEYWORDS: Neurons

MESH TERMS: pathology

Chemical & Substance for Abstract: Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease. Information

Substance Name: Atp7a protein, mouse

Registry Number: EC 3.6.3.4

Grant and Affiliation Information for Altered ATP7A expression and other compensatory responses in a murine model of Menkes disease.

AFFILIATION: University of Connecticut Health Center, Department of Neuroscience, Academic Research Building (E)-4047(1), 263 Farmington Avenue, Farmington, CT 06030-3401, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: T32 GM008607-08

ACRONYM: GM

MEDLINETA: Neurobiol Dis

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