FAC1, A NOVEL GENE IDENTIFIED WITH THE MONOCLONAL-ANTIBODY ALZ50, IS DEVELOPMENTALLY-REGULATED IN HUMAN BRAIN

The monoclonal antibody Alz50 recognizes both neurofibrillary patholog y associated with Alzheimer's disease and subplate neurons in the deve loping human brain. To attempt to identify Alz50 antigens expressed du ring development, a human fetal brain cDNA library was immunoscreened. A positive clone was isolated and sequenced. The clone represents a n ovel gene named FAC1 (Fetal Alz-50-Reactive Clone 1). The FAC1 gene is located on human chromosome 17 and is conserved across species. In th e human fetal brain, the FAC1 gene product is abundantly expressed and the protein is located both in the nucleus and the cytoplasm of cells throughout the developing cortex. Decreased levels of FAC1 protein ar e observed in adult brain by immunoblot analysis. By immunocytochemist ry, the FAC1 protein is almost exclusively localized in the nucleus of neurons in the adult neocortex. Therefore, expression of the FAC1 gen e is developmentally regulated and the cellular localization of the pr otein product is altered during development.