The reeler (rl) mutant mouse has provided important insights to cortical development and function. This project is designed to elucidate the site(s) of mutant gene acton in the rl mouse, and relate the structural abnormalities of the mutation to behavioral deficits. Three approaches to the problem of where the rl gene acts will be made: 1) We can test whether an alteration of the extracellulr milieu is the means by which the rl gene exerts is action by transplantion of early embryonic rl cerebella or hippocampal formations. 2) Reeler reaction goes both right and left normal chimeric mice will be created to analyze rl gene action relative to cerebellar granule cells. The ichthyosis phenotype of centrally clumped heterochromatin will be used in one component of the chimera to analyze granule cell populations. 3) I will use a new cell marker in chimeras that should label all cell types and allow me to study the site of mutant gene action in other neuronal and supporting cells in rl reaction goes both right and left normal chimeric brains. The varying expression of the rl phenotype inherent in chimeric mice will permit me to correlate performance of hippocampal-specific behavioral tasks (radial arm maze, spontaneous alternation and two-way avoidance) with both the cytoarchitectonics of the hippocampal subfields and patterns of cholinergic innervation and mossy fiber distribution. After behavioral testing, chimeric mice and controls will be perfused and their brains sectioned for the sequential histological processing and analysis of cerebellar granule cells and hippocampal cytoarchitectonics (Nissl stain), hippocampal cholinergic innervation (acetylcholinesterase histochemistry), and mossy fiber distribution (Timm's stain for heavy metals). The three long term goals of this work are to: 1) Use the information gained about the site of rl gene action to better understand and explain development and abnormalities of the mammalian central nervous system, 2) Establish the use of a new cell marker to reliably study the whole range of nervous system cells in chimeras, and 3) Use the mutant reaction goes both right and left normal chimera as a model system to integrate our knowledge of genetic, anatomical and behavioral phenomena.
| Goldowitz, D (1987) Cell partitioning and mixing in the formation of the CNS: analysis of the cortical somatosensory barrels in chimeric mice. Brain Res 432:1-9 |
| Goldowitz, D; Koch, J (1986) Performance of normal and neurological mutant mice on radial arm maze and active avoidance tasks. Behav Neural Biol 46:216-26 |
