Vol. 184, No. 2, 1992 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS April 30, 1992 Pages 1082-1087 THE DROSOPHILA PER GENE HOMOLOGS AR.E EXPRESSED IN MAMMALIAN SUPRACHlASMATIC NUCLEUS AND HEART AS WELL AS IN MOLLUSCAN EYES Thomas Maler *,+,I , ?btin R. Ralph’, Reginald Y. Gorczynski’, Harvey Moldofsky*, Brian F. O’?Iowd% and Daisy Chin Du* * Department of Psychiatry, Toronto Western Hospital, Toronto, Canada department of Clinical Biochemistry, University of Toronto, Toronto, Canada # Department of Psychology, University of Toronto, Toronto, Canada G Departments of Surgery and Immunology, University of Toronto, Toronto, Canada % Addiction Research Foundation, Ontario, Canada Received March 20, 1992 This study presents evidence for the conservation of Drosophila per gene homologs in mammalian DNA and for their expression in a number of tissues which are involved in various aspects of circadian timekeeping. Distinct 5 kb sequences, which hybridized to a non repetitive fragment of the Drosophila per gene under stringent conditions, were detected by Southern blotting. Sequences homologous to per gene of Drosophila were also amplified from rat and mouse brain cDNA libraries and from a mouse anterior hypothalamus and human hypothalamus libraries. Degenerate PCR primer design was based on conserved segments of the per protein. The per homologs were shown directly (by RT-PCR) to be expressed in hamster and mouse SCN, in hamster heart and in Aplysia and Bulla eyes. % 1992 Acadrmlc PTP55, I” Circadian rhythms are ubiquitous in plants as well as in animals. They control a number of important periodic events, yet little is known about the cellular mechanisms that underlie the circadian behaviour in mammals. The identification of important molecules and genes, which are involved in the control of circadian rhythmicity, has in the past been aided by the isolation of mutants exhibiting disruption of some aspects of their biological rhythms (1,2,3,4). The best well known example is the per gene (and its products) of Drosophila melanogaster. Mutations in this gene are known to shorten (per?, lengthen (per”) or completely abolish (per”) circadian rhythms in the fly (5). Transformation of per’ flies with per gene restores its circadian rhythms and the period of the restored rhythms is dependent on the gene dosage (6). Furthermore, Hardin et al (7) and Zerr et aI (8) have demonstrated that the level of per protein product undergoes circadian oscillation and they further showed that the nature of this oscillation lies in the cycling of the level of the per mRNA. They suggested, that the activity of the per-encoded protein constitutes a feedback loop through which the cycling of its own mRNA is controlled. ll’o whom correspondence should be addressed at T&t Research, 44 George Street, Etobicoke, Ontario, Canada MN 2S2. 0006-291X/92 $1.50 Copyright 0 1992 by Academic Press, Irzc. All rights of reproduction in any form reserved. 1082