Letter to the Editor this criteria correspond to known functional groups of A Unified Nomenclature System for receptors. This procedure yields six subfamilies. All the the Nuclear Receptor Superfamily unusual receptors that contain only one of the two conserved domains (C or E) were grouped into a separate subfamily (subfamily 0) irrespective of their evolutionary Nuclear hormone receptors (NRs) are important tranorigin. Within subfamilies, groups of receptors are descriptional regulators involved in widely diverse physiofined as the most internal branches with bootstrap vallogical functions such as control of embryonic developues above 90%. In this nomenclature system, the numment, cell differentiation, and homeostasis (Gronemeyer ber of a given receptor inside a group does not carry and Laudet, 1995; Mangelsdorf et al., 1995). In addition, any specific information. In many cases these groups these molecules are extremely important in medical recontain arthropod and vertebrate members. The various search since a large number of them are implicated in homologs of the same gene in invertebrates (e.g., Drodiseases such as cancer, diabetes, or hormone resissophila and Caenorhabditis) have the same name. It is tance syndromes. Some of the NRs act as ligand-inducible transcription factors, while a large number of them have no defined ligand and are hence described as "orphan" receptors (Enmark and Gustafsson, 1996). Over the last decade, workers in the field have described more than 300 sequences of NRs using an increasingly complex and baroque nomenclature. The existence of several names for the same gene is an acute problem for the orphan receptors, which often cannot be described by their function, particularly at the moment of their discovery. As discussed during the Seventh International CBT Symposium on "Nuclear Orphan Receptors" in Huddinge, Sweden (September 9-12, 1995), this plethora of names has become more and more confusing and now constitutes a barrier for understanding of newly acquired knowledge to researchers outside as well as within the field. For that reason, four of us (V. L., J. A., J.-A. G., and W. W.) agreed to form a committee for the nomenclature of NRs. It is the purpose of this paper to recommend names for the subfamilies and groups of receptors based on a phylogenetic tree connecting all known NR sequences. This system, based on the evolution of the two well-conserved domains of NRs (the DNA-binding C domain and the ligand-binding E domain), offers a practical and significant framework to which subsequent genes can be easily added. The resulting nomenclature has now been endorsed by over 40 scientists 1 many of whom contributed to defining the nomenclature and to preparing this letter. This nomenclature has been discussed with the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). A subcommittee of NC-IUPHAR entitled "Nuclear Receptors" will be set up to further clarify receptor nomenclature to integrate structure and function.A summa...

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A single-base deletion in the single-copy vasopressin gene is the cause of diabetes insipidus in the homozygous Brattleboro rat (di/di). It results in the synthesis of an altered vasopressin precursor of which the axonal transport is blocked. Paradoxically, a small number of solitary hypothalamic neurons displays all the immunoreactivities of the wildtype vasopressin precursor (i.e., vasopressin, neurophysin, and a glycopeptide). In the present paper we provide evidence that these neurons have undergone a switch to a genuine heterozygous (di/+) phenotype; i.e., they contain the immunoreactivities of both the wild-type and the mutated vasopressin precursors. In the neural lobe, glycopeptide fibers are also present, showing that axonal transport of the wild-type precursor is restored. Moreover, the number of neurons displaying this di/+ phenotype increases markedly and in a linear way (from 0.1% up to 3% of the vasopressin cells) with age. These findings indicate that after mitotic division has ceased, genomic alterations occur in somatic neurons in vivo. The molecular event generating the di/+ phenotype in the di/di animal could involve a somatic intrachromosomal gene conversion between the homologous exons of the vasopressin and the related oxytocin genes.Since its discovery in 1961 the diabetes insipidus Brattleboro rat (phenotype, di/di) with impaired vasopressin (VP) synthesis has become an extremely useful model for many disciplines to study hypothalamic diabetes insipidus and to clarify problems related to the physiology ofVP (1). The di/di rat exhibits a recessively inherited hypothalamic diabetes insipidus due to a single-base deletion in the unique VP gene (2). This point mutation results in the synthesis of an altered VP precursor whose C-terminal glycopeptide (GP) moiety, because of a frame-shift, is replaced by a nonglycosylated amino acid sequence (2). As a consequence intracellular processing and axonal transport toward the neural lobe ofthe mutant precursor are blocked. Paradoxically, a small number of solitary hypothalamic neurons seems to express wild-type VP gene products that are transported toward the neural lobe (3-5). To explain these results, an intrachromosomal gene conversion between the homologous exons of the VP and oxytocin (OT) genes has been proposed (6). To (termed, di/+) and that the number of these neurons increases linearly with age. The findings imply that genomic alterations occur after mitotic division has ceased and are compatible with the intrachromosomal gene conversion within the VP/OT gene locus. MATERIALS AND METHODSAnimals and Fixation. Male and female di/di Brattleboro rats of 18 days to 79 weeks of age were obtained from Harlan (Zeist, The Netherlands) or homebred. They were individually checked for water consumption and diuresis. The animals were anaesthetized with Nembutal (60 mg/kg, i.p.) and perfused intracardially with 0.9% NaCl (shortly) and then with 0.1 M sodium phosphate-buffered 4% (wt/vol) paraformaldehyde (pH 7.4) and pieces of tissue then wer...

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