| Microarray technology, aimed at creating a method of assaying transcript levels within a cell at a given point in time, has been utilized in the investigation of normal as well as abnormal cellular functioning. Through advancements in expression assaying methods and the sequencing of the full murine genome it is now possible to evaluate the intracellular RNA environment at any selected time. Two different gene expression profiling platforms (cDNA microarrays and Affymetrix oligonucleotide arrays) are herein used to investigate gene expression changes during normal development and to define alterations in two genetic disorders. cDNA microarrays containing specific murine brain transcripts were created to facilitate higher resolution insight into the cellular processes which guide and correlate normal brain development in a model organism. With the evolution of microarray technology (Affymetrix oligonucleotide arrays) this highly reproducible and standardized platform was utilized to gain insight into the central nervous system disorders Neurofibromatosis Type 1 (NF1) and Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency. The known primary genetic defect characteristic of NF1 leads to a loss of functional neurofibromin protein which can now be directly linked to decreased long term potentiation and subsequent deficiencies in cognition and learning. SSADH deficiency has a known primary genetic lesion affecting the GABA-glutamate axis, and through Affymetrix microarray analysis effects of this enzyme deficiency can now explain the resultant epileptogenesis. In this well-characterized murine model the GABA-glutamate axis and eventual dysmyelination are the primary pathogenic events related to seizures, offering insight into the correlated human disorder. Microarray technologies, ranging from the manually produced cDNA microarrays to the standardized Affymetrix oligonucleotide microarrays, were herein utilized in the investigation of normal murine development and two neurologically dysfunctional models. |
