TRANSGENIC TARGETING OF NEUROENDOCRINE PEPTIDE GENES IN THE HYPOTHALAMIC-PITUITARY AXIS

A large number of neuroendocrine peptide genes have been tested for their ability to target expression to the hypothalamus and pituitary in transgenic mice. This has resulted in a number of powerful applications, for example, ablation or immortalization of specific cell types, and analysis of transcription regulatory sequences. The greatest amount of success in targeting cells of the neuroendocrine axis has been in the pituitary and has utilized regulatory sequences of genes that are normally expressed in pituitary. Greater difficulties have been encountered in directing expression to specific neurons in the hypothalamus. A primary goal of this review is to consider collectively the data obtained by a number of laboratories in order to draw conclusions about the general sequence requirements for achieving cell-specific expression. The data suggest that the mechanisms controlling cell-specific expression of neuropeptide genes in the hypothalamus are complex and involve multiple regulatory elements that may reside within the gene or many kilobases away from the promoter. These elements act positively and negatively in different cells to enhance or restrict expression, and may include sequences that shield a transgene from regulatory influences of other genes near the point of chromosomal insertion.