Oregon Health & Science University

Wenbiao Chen

Roger D Cone

Bruce A Boston

Dongsi Lu

Robert A Kesterton

Wei Fan

Malcolm J Low

The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian melanocortin receptors. The invention provides a panel of such transformed mammalian cells expressing melanocortin receptors for screening compounds for receptor agonist and antagonist activity. The invention also provides methods for using such panels of melanocortin receptor-expressing mammalian cells to specifically-detect and identify agonists and antagonists for each melanocortin receptor, as well as patterns of agonist and antagonist activity of said compounds for the class of melanocortin receptors. Such screening methods provide a means for identifying compounds with patterns of melanocortin agonist and antagonist activity which is associated with the capacity to influence or modify metabolism and behavior, particularly feeding behavior.

Methods and reagents for discovering and using mammalian melanocortin receptor agonists and antagonists to modulate feeding behavior in animals

This invention provides methods and reagents for developing naturally-occurring and synthetic agonists and antagonists specific for a mammalian melanocortin receptor, and the use of such agonists and antagonists for treatment and alleviation of dysfunction and disease. The invention specifically provides reagents and methods for developing naturally-occurring and synthetic agonists and antagonists specific for a mammalian melanocortin receptor termed MC5-R. The naturally-occurring and synthetic agonists and antagonists specific for the MC5-R receptor are provided by the invention for the treatment, control, amelioration and alleviation of diseases, and dysfunctional and abnormal states related to thermoregulatory disorders, as well as other diseases relating to exocrine gland disorders, including lacrimal gland dysfunction and sebaceous gland disorders including acne and other skin problems. Also provided by the invention are nucleic acids, constructs, vectors and methods for producing an animal bearing a genetically-disrupted endogenous MC5-R melanocortin receptor, in both the heterozygous and homozygous condition, preferably a rodent and most preferably a mouse. Rodents bearing genetically disrupted MC5-R genes homozygously, termed &ldquo;gene knockout&rdquo;rodents in the art, are also advantageously provided.

Mammalian melanocortin receptors and uses

The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian melanocortin receptors. The invention provides a panel of such transformed mammalian cells expressing melanocortin receptors for screening compounds for receptor agonist and antagonist activity. The invention also provides methods for using such panels of melanocortin receptor-expressing mammalian cells to specifically detect and identify agonists and antagonists for each melanocortin receptor, as well as patterns of agonist and antagonist activity of said compounds for the class of melanocortin receptors. Such screening methods provide a means for identifying compounds with patterns of melanocortin agonist and antagonist activity which are associated with the capacity to influence or modify metabolism and behavior, particularly feeding behavior.

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Portland, OR, United States of America

Wenbiao Chen