Expression of genes encoding neuropeptides and enzymes in the brain, with emphasis on the hypothalamus, are being studied. We successfully created a knock-out of the oxytocin gene in mice through homologous recombination. These mice demonstrate that oxytocin is absolutely required for milk ejection, but not mammary gland development, fertility or parturition. We are conducting further studies to see how the absence of oxytocin affects mouse behavior and reproduction. Initial studies indicate that some aspects of aggressive behavior are decreased. We have determined that oxytocin participates in the regulation of mammary gland celllular development and apoptosis. Finally, we have determined how to use the OT gene to express in a cell-specific way foreign genes in the mouse brain.This past year, we have generated homozygous mice for the vasopressin 1b receptor knock- out. They appear to be growing mormally and we should begin studying their response to stress shortly. We are also continuing our research on the putative Rho-GAP, C1, found in the developing brain and adult thymus and spleen in partciular. C1 may be involved in cell mobility and process formation and retraction. We also completed work on the human PG10.3 gene, renamed Spacercan, which is a novel human interphotoreceptor matrix hyaluronan-binding proteoglycan synthesized by photoreceptors and pinealocytes. Its potential involvement in macular degeneration is being exami - oxytocin, vasopressin, hyptothalamus, stress, pituitary, Rho-GAP, C1
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