We suggest a model in which a hierarchy of controls is exerted on the family of odorant receptor genes to assure that a sensory neuron expresses a single receptor from a family of 1000 genes. We propose that a cis-regulatory element directs the stochastic expression of only one gene from a large array of linked receptor genes. Moreover, only one allelic array encoding multiple receptor genes is active in an individual neuron. We demonstrate that in a neuron expressing a given receptor, expression derives exclusively from one allele. In addition, we observe that alleles encoding the odorant receptors are replicated asynchronously, a phenomenon consistently associated with allelic inactivation. This model, involving inactivation of one allelic array and cis control of the active array, provides a mechanism such that individual neurons express one or a small number of receptors.
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We thank Y. Sun for excellent technical assistance and P. J. K~sloff for assistance in preparing the manuscript. We also thank T. Livelli for help with the olfactory epithelium dissociations and for helpful discussions. We are grateful to Dr. V. Chapman for providing mice from interspecies crosses. We thank Drs. V. Chapman, T. Jessell, P. Mom-baerts, P. Sklar, and A. Tomlinson for helpful discussions and critically reading the manuscript. This work was supported by the Howard Hughes Medical Institute, by a Clinical Investigator Development award (D000082) from the National Institute of Deafness and Communicative Disorders (A. C.), and by grants from the National Institutes of Health (H. C.), the Israel Academy of Sciences (H. C.), and the Israel Cancer Research Fund (H. C.).