The brain‐specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain

Medientyp: E-Artikel
Titel: The brain‐specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain
Beteiligte: Schmitt, Angelika; Gofferje, Viktor; Weber, Melanie; Meyer, Jobst; Mössner, Rainald; Lesch, Klaus‐Peter
Erschienen: Wiley, 2003
Erschienen in: Glia
Sprache: Englisch
DOI: 10.1002/glia.10304
ISSN: 0894-1491; 1098-1136
Schlagwörter: Cellular and Molecular Neuroscience ; Neurology
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Beschreibung: <jats:title>Abstract</jats:title><jats:p>The human <jats:italic>MLC1</jats:italic> gene (also known as <jats:italic>KIAA0027</jats:italic> and <jats:italic>WKL1</jats:italic>) and its murine orthologue (<jats:italic>Mlc1</jats:italic>) encode a putative transmembrane protein expressed primarily in brain. Recessive mutations within human <jats:italic>MLC1</jats:italic> cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), whereas a missense mutation resulting in a methionine substitution within a transmembrane leucine string of MLC has been implicated in catatonic schizophrenia in a large pedigree. To gain insight into the function of the MLC protein and to elucidate the pathophysiology of these severe neurodegenerative disorders, information on the cellular and regional distribution of the murine <jats:italic>Mlc1</jats:italic>, as well as the developmental pattern of <jats:italic>Mlc1</jats:italic> expression in brain, is required. Using in situ hybridization (ISH), <jats:italic>Mlc1</jats:italic> mRNA was exclusively detected in glial cells of the adult murine brain, such as astrocytes, Bergmann glia, and ependymal cells. ISH, Northern blot analysis, and quantitative real‐time polymerase chain reaction (PCR) demonstrated that <jats:italic>Mlc1</jats:italic> mRNA is broadly distributed in the adult mouse brain, with highest concentrations of expression in the cerebellum and olfactory bulb. Furthermore, differential expression patterns during brain development were revealed. Overall brain <jats:italic>Mlc1</jats:italic> mRNA concentrations exhibited a substantial increase in the perinatal period reaching adult concentrations at postnatal day 5. At the cellular level, highest <jats:italic>Mlc1</jats:italic> expression was found during the pre‐ and perinatal period in multipotential neural precursor cells, especially in the subventricular zone of the lateral ventricle, whereas in adulthood highest Mlc1 mRNA concentrations were revealed in Bergmann glia cells. Because the temproal expression profile of <jats:italic>Mlc1</jats:italic> indicates that, in contrast to developing and mature astrocytes, oligodendrocytes are devoid of <jats:italic>Mlc1</jats:italic> expression, white matter tract abnormalities observed in these disorders may result from a primary astrocytic defect. Detailed information on <jats:italic>Mlc1</jats:italic> expression in brain is likely to lead to a better understanding of Mlc1 involvement in the pathogenesis of both MLC and catatonic schizophrenia. © 2003 Wiley‐Liss, Inc.</jats:p>

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