The General Hospital Corporation

Other

Steven M Reppert

Takashi Ebisawa

Valentin K Gribkoff

Mark Zylka

David R Weaver

Xiaowei Jin

Sriram Sathyanarayanan

Kazuhiko Kume

Lauren Shearman

Disclosed are cDNAs and DNAs encoding high-affinity melatonin 1a and 1b receptors and the recombinant polypeptides expressed from such cDNAs. The recombinant receptor polypeptides, receptor fragments and analogs expressed on the surface of cells are used in methods of screening candidate compounds for their ability to act as agonists or antagonists to the effects of interaction between melatonin and high-affinity melatonin receptor. Agonists are used as therapeutics to reentrain endogenous melatonin rhythms as a means of treating circadian rhythm disorders in humans and control reproductive cycles in seasonally breeding animals. Antagonists are used as therapeutics to control the initiation or timing of puberty in humans. Antibodies specific for a high-affinity melatonin receptor (or receptor fragment or analog) and their use as a therapeutic are also disclosed.

High-affinity melatonin receptor and uses thereof

The invention is based, in part, on the discovery that the CRY proteins and the PER2 protein function as important modulators of mammalian circadian rhythm. The invention includes methods of modulating the circadian rhythm and identifying compounds that modulate the circadian rhythm.

Methods for identifying compounds which modulate circadian rhythm

Disclosed are mice containing a targeted disruption of various melatonin receptor subtypes, and methods of using the mice to identify agonists and antagonists of melatonin.

Melatonin receptor-deficient mice and uses thereof

Disclosed are DNAs encoding melatonin 1a receptor gene promoter regions, recombinant polypeptides expressed from such DNAs, and methods of using such expression constructs to screen for promoter activators or inhibitors. Transcriptional activators are useful as therapeutics to reentrain endogenous melatonin rhythms as a means of treating circadian rhythm disorders in humans and control reproductive cycles in seasonally breeding animals. Transcriptional inhibitors are useful as therapeutics to control the initiation or timing of puberty in humans.

Melatonin 1a receptor gene regulatory regions an uses thereof

Melatonin 1A receptor gene regulatory regions and uses thereof

DNA encoding high-affinity melatonin receptors

Disclosed are cDNAs encoding A.sub.2b -adenosine receptors and the recombinant proteins expressed from such cDNAs. The recombinant receptor and receptor fragments and analogs are used in methods of screening candidate compounds for their ability to antagonize interaction between adenosine and an A.sub.2b -adenosine receptor; antagonists are used as therapeutics to reduce inflammatory gastrointestinal tract diseases or asthma. Antibodies specific for A.sub.2b -adenosine receptor (or receptor fragment or analog) and their use as a therapeutic and diagnostic are also disclosed.

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Newton, MA, United States of America

Steven M Reppert