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Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF-B in myelinating tracts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2003 (English)In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 41, no 3, 276-89 p.Article in journal (Refereed) Published
Abstract [en]

Platelet-derived growth factor (PDGF) influences the generation of neurons and glia during embryogenesis and in early postnatal life. In an attempt to determine the consequences of an overexpression of PDGF-B during the first weeks of life, we targeted transgenic expression of a human PDGF-B cDNA to myelinating tracts using the promoter region of the myelin basic protein (MBP) gene. Transgenic mRNA and protein were expressed in the brain and the expression profile of the human PDGF-B during early postnatal development closely paralleled that of the endogenous mouse MBP gene. The gross morphological appearance of transgenic brains was normal but at the cellular level several phenotypic alterations could be identified. In white matter tracts such as the corpus callosum and cerebellar medulla, there was a marked hypercellularity. The number of oligodendrocyte precursors was increased and astrocytes were more abundant. In adult mice carrying the MBP-PDGF-B transgene, however, myelination appeared normal and the amount of oligodendrocytes was similar to that of control littermates. In addition to the phenotypic alterations in the brain, investigation of eye structure revealed a striking disorganization of retinal architecture. The retina was folded with cells collected in papillar or follicular-like structures. Retinal whole mount preparations after India ink perfusion revealed capillary disorganization with large-caliber vessels supporting only a few fine branches. Our observations strengthen the notion that PDGF is an important effector molecule in postnatal CNS development.

Place, publisher, year, edition, pages
2003. Vol. 41, no 3, 276-89 p.
Keyword [en]
transgenic mice, myelin basic protein, eye, development
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-64201DOI: 10.1002/glia.10191PubMedID: 12528182OAI: oai:DiVA.org:uu-64201DiVA: diva2:92112
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-11-30Bibliographically approved

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Forsberg-Nilsson, KarinWestermark, Bengt

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