Clark, R.F., P. Nowotny, C.J. Jones, K. Philips, and A.M. Goate. 1997. "The use of Drosophila melanogaster as a model organism to characterize the presenilin gene associated with early-onset Alzheimer's disease." American Journal of Human Genetics 61(4):A169.
Genetic linkage studies in early-onset familial Alzheimer's disease (FAD) have determined that mutations in the human presenilin genes 1 and 2 (PS-1 and PS-2) are the major cause of the disease. While it has been reported that Aβ production is abnormal in fibroblasts from families carrying PS-1 and PS-2 mutations, and the homologous protein SEL-12 in C. elegans affects Notch signaling, the function of these genes are presently unknown. To understand more about the biology and function of the presenilin genes, we used the very high conservation of the presenilin genes in mammals and the sel-12 gene in nematode to clone the homologous gene in Drosophila melanogaster. Drosophila is an ideal model organism as biochemical, cytological, and genetic approaches are all readily available and all easily manipulated. Sequencing of cDNA and genomic clones of the Drosophila presenilin gene reveals that the encoded protein is 508 amino acids (with additional splice products producing proteins of 527 and 541 amino acids) and is 51% identical to SEL-12, 52% identical to human PS-1, and 52% to human PS-2. Similar to SEL-12, the predicted protein contains six or eight transmembrane domains. The gene has been mapped to polytene chromosomes and thus a genetic approach will be taken to look at the consequence of deletion of the presenilin gene.