Enlarged lateral ventricles and aberrant behavior in mice overexpressing PDGF-B in embryonic neural stem cells.
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.
Niklasson
Mia
M
Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden.
Bergström
Tobias
T
Zhang
Xiao-Qun
XQ
Gustafsdottir
Sigrun M
SM
Sjögren
Maria
M
Edqvist
Per-Henrik
PH
Vennström
Björn
B
Forsberg
Maud
M
Forsberg-Nilsson
Karin
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000254:growth & development; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000494:pharmacology; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology; D064231:Nestin; D009474:Neurons / Q000166:cytology*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D012737:Sex Factors
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D020574:Proto-Oncogene Proteins c-sis