Enlarged lateral ventricles and aberrant behavior in mice overexpressing PDGF-B in embryonic neural stem cells
| Autor: | Tobias Bergström, Maria Sjögren, Xiao-Qun Zhang, Per-Henrik Edqvist, Björn Vennström, Sigrun M. Gustafsdottir, Mia Niklasson, Maud Forsberg, Karin Forsberg-Nilsson |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Genetically modified mouse Transgene Embryonic Development Mice Transgenic Nerve Tissue Proteins Biology Nestin Mice Paracrine signalling Sex Factors Intermediate Filament Proteins Lateral Ventricles Animals Progenitor cell Autocrine signalling Embryonic Stem Cells Neurons Behavior Animal Brain Proto-Oncogene Proteins c-sis Cell Biology Embryonic stem cell Neural stem cell Cell biology Gene Expression Regulation Immunology Female |
| Zdroj: | Experimental Cell Research. 316:2779-2789 |
| ISSN: | 0014-4827 |
| Popis: | Platelet-derived growth factor (PDGF) is important in central nervous system (CNS) development, and aberrant expression of PDGF and its receptors has been linked to developmental defects and brain tumorigenesis. We previously found that neural stem and progenitor cells in culture produce PDGF and respond to it by autocrine and/or paracrine signaling. We therefore aimed to examine CNS development after PDGF overexpression in neural stem cells in vivo. Transgenic mice were generated with PDGF-B under control of a minimal nestin enhancer element, which is specific for embryonic expression and will not drive adult expression in mice. The resulting mouse showed increased apoptosis in the developing striatum, which suggests a disturbed regulation of progenitor cells. Later in neurodevelopment, in early postnatal life, mice displayed enlarged lateral ventricles. This enlargement remained into adulthood and it was more pronounced in male mice than in transgenic female mice. Nevertheless, there was an overall normal composition of cell types and numbers in the brain and the transgenic mice were viable and fertile. Adult transgenic males, however, showed behavioral aberrations and locomotor dysfunction. Thus, a tightly regulated expression of PDGF during embryogenesis is required for normal brain development and function in mice. |
| Databáze: | OpenAIRE |
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