Characterization of Regulatory Regions Elements in Neuronal Genes

The primary aim, indeed the sine qua non, of transgenic studies is to direct expression of particular genes to specific groups of cells within heterogeneous cellular systems. Cell/tissue-specific expression is both an essential prerequisite to functional analysis of transgene expression and a requirement of studies in which the role of cis-acting regulatory elements are investigated in an appropriate cellular context; i.e., in the presence of corresponding trans-acting factors. The multiplicity of cell-types in the mammalian brain, each exhibiting unique patterns of gene expression, represents the extreme example in biology of a complex system in which precise genetic control is essential to permit the variety of phenotype. Although cell-specific transgene expression has been attained in a number of studies on the mouse central nervous system (CNS), it is not possible to make specific recommendations on the design of recombinant gene constructs for use in transgenic studies on the brain. On the contrary, comparison of different experiments has revealed considerable variation in the size and make-up of DNA constructs that appear to be required to direct neuronal expression of particular genes. However, the literature is now of sufficient breadth to allow some useful generalizations to be drawn and questions may reasonably be posed regarding the size and composition of DNA constructs.

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