In vivo inactivation of pRb , p107 and p130 in murine neuroprogenitor cells leads to major CNS developmental defects and high seizure rates
| Autor: | German P. Garcia-Fresco, Julie A. McLear, Manzoor A. Bhat, Terry Van Dyke |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Central Nervous System
SV40 large T antigen Transgene Green Fluorescent Proteins Central nervous system Population Fluorescent Antibody Technique Mice Transgenic Nerve Tissue Proteins Retinoblastoma-Like Protein p107 Biology Hippocampal formation Nestin Mice Cellular and Molecular Neuroscience Intermediate Filament Proteins Seizures medicine Animals Humans Progenitor cell education Molecular Biology Neurons education.field_of_study Behavior Animal Retinoblastoma-Like Protein p130 Reverse Transcriptase Polymerase Chain Reaction Stem Cells Cell migration Cell Biology Embryo Mammalian Embryonic stem cell Cell biology medicine.anatomical_structure Animals Newborn embryonic structures Neuroscience |
| Zdroj: | Molecular and Cellular Neuroscience. 33:260-273 |
| ISSN: | 1044-7431 |
| DOI: | 10.1016/j.mcn.2006.07.012 |
| Popis: | Nestin-positive cells were targeted for pRb, p107 and p130 (pRb f ) inactivation by expression of T 121 , a truncated SV40 large T antigen that selectively binds to and inactivates pRb f . Cre expression was initiated under GFAP control, resulting in T 121 expression restricted to neuroprogenitor cells beginning at embryonic day 11.5 (E11.5). Bi-transgenic embryos showed aberrant central nervous system (CNS) cell proliferation and apoptosis by E13.5. Defects in cortical development were evident with primary effects resulting in depletion of neural progenitors and aberrant cellular migration. Consequently, juvenile and adult brain morphology was reproducibly abnormal, including disorganization of neocortical, hippocampal and cerebellar regions. These aberrations resulted in behavioral phenotypes, including ataxia and seizures. The data indicate that inactivation of pRb f in radial glial cells, a population of neuroprogenitor cells, leads to specific disruptions in CNS patterning. The neuroprogenitor-restricted transgene expression provides a model in which to explore both developmental mechanisms and functional neurological outcomes. |
| Databáze: | OpenAIRE |
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