The chromosomal distribution of mouse odorant receptor genes.

Sullivan, Stephen N.; Adamson, M. C.; Ressler, Kerry J.; Kozak, Christine A.; Buck, Linda B.

doi:10.1073/pnas.93.2.884

Cited by 199 publications

(171 citation statements)

References 35 publications

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“…It does not preclude the recognition of a particular class of odorants by different subfamilies, however (11). OR genes can be found at many chromosomal loci, but highly related ORs often reside at the same locus (7,8,(19)(20)(21)(22)(23)36), raising the possibility that different parts of the genome are, to some degree, involved in the recognition of different types of odorants.…”

mentioning

confidence: 99%

The human olfactory receptor gene family

Malnic

Godfrey

Buck

2004

Proc. Natl. Acad. Sci. U.S.A.

524

357

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Humans perceive an immense variety of chemicals as having distinct odors. Odor perception initiates in the nose, where odorants are detected by a large family of olfactory receptors (ORs). ORs have diverse protein sequences but can be assigned to subfamilies on the basis of sequence relationships. Members of the same subfamily have related sequences and are likely to recognize structurally related odorants. To gain insight into the mechanisms underlying odor perception, we analyzed the human OR gene family. By searching the human genome database, we identified 339 intact OR genes and 297 OR pseudogenes. Determination of their genomic locations showed that OR genes are unevenly distributed among 51 different loci on 21 human chromosomes. Sequence comparisons showed that the human OR family is composed of 172 subfamilies. Types of odorant structures that may be recognized by some subfamilies were predicted by identifying subfamilies that contain ORs with known odor ligands or human homologs of such ORs. Analysis of the chromosomal locations of members of each OR subfamily revealed that most subfamilies are encoded by a single chromosomal locus. Moreover, many loci encode only one or a few subfamilies, suggesting that different parts of the genome may, to some extent, be involved in the detection of different types of odorant structural motifs

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mentioning

confidence: 99%

The human olfactory receptor gene family

Malnic

Godfrey

Buck

2004

Proc. Natl. Acad. Sci. U.S.A.

524

357

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“…1A). The construct was inserted via homologous recombination between the well characterized OR genes M71 and M72 (20,21). The M71 and M72 receptor genes are expressed in a more dorsal zone of the OE (zone I) than M4 (zone II) (13), and cells expressing M71 or M72 project axons to glomeruli in a dorsal region of the OB (13,(22)(23)(24)(25).…”

Section: Resultsmentioning

confidence: 99%

“…We targeted an OR M4 promoter-driven reporter to a gene cluster comprising Ϸ100 OR genes (20,21). The expression construct consisted of 2.4 kb of M4 promoter sequence, the native transcription start site, and a 4-kb intron followed by a Tau-LacZ reporter (13).…”

Section: Resultsmentioning

confidence: 99%

A feedback mechanism regulates monoallelic odorant receptor expression

Lewcock

Reed

2004

Proc. Natl. Acad. Sci. U.S.A.

241

229

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In olfactory neurons, expression of a single odorant receptor (OR) from a repertoire of >1,000 genes is required for odor coding and axonal targeting. Here, we demonstrate a role for OR protein as an essential regulator in the establishment of monoallelic OR expression. An OR-promoter-driven reporter expresses in a receptor-like pattern but, unlike a native OR, is coexpressed with an additional OR allele. Expression of a functional OR from the identical promoter eliminates expression of other OR alleles. The presence of an untranslatable OR coding sequence in the mRNA is insufficient to exclude expression of a second OR. Together, these data identify the OR protein as a critical element in a feedback pathway that regulates OR selection.T he mammalian olfactory system detects odors with remarkable sensitivity while decoding the complex odorant stimuli present in the environment. Populations of olfactory neurons with similar response profiles generate patterned activity within the olfactory bulb (OB) and lead to the perception of a given odor. These cellular responses are defined by the selective expression of seven-transmembrane odorant receptor (OR) proteins (1).Each olfactory neuron expresses only one allele of an individual OR gene from Ͼ1,000 related genes dispersed throughout the genome, a process termed monoallelic expression (2-4). The neurons expressing a particular OR reside in one of multiple zones defined by their dorsal-medial to ventral-lateral position in the olfactory epithelium (OE) (5, 6). These OR expression zones contribute broad topographic organization for the axons of olfactory neurons as they target the OB (5,7,8). ORs also play an important role in olfactory axon pathfinding (9, 10). Neurons that express the same OR, while interspersed with neurons expressing other ORs in the epithelium, project axons that converge to a small number of stereotyped glomeruli in the OB (11, 12). A transgene comprised of proximal OR promoter sequences is in many cases sufficient to recapitulate normal expression (13,14), although the transgene integration site can significantly influence reporter expression. This variability has confounded the elucidation of the processes that contribute to monoallelic, zonal OR expression.The monoallelic expression of ORs is critical to the establishment of the functionally distinct neuronal populations required for odor discrimination and organization of axonal projections to the OB (15, 16). This highly regulated expression could be achieved through a probabilistic promoter selection mechanism that is independent of the production of functional OR protein (10). Alternatively, OR protein or mRNA could initiate a feedback signal that ensures monoallelic expression.To determine whether monoallelic OR expression depends on feedback regulation, we targeted an OR promoter-driven reporter to a defined, reproducible transgene insertion site amid a cluster of ORs. This approach alleviates transgenic variability while facilitating analysis of potential coexpression with adjacent ORs...

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“…In mouse OE these zones are referred to as zones 1-4, with zone 1 being most dorsal/ medial located and zone 4 most ventral/lateral located. OR genes M40, K20, L45, and A16 were previously shown to be expressed in zones 1, 2, 3, and 4, respectively (10,16). Importantly, in situ hybridization revealed that RNCAM expression was restricted in OE to cover exactly zones 2, 3, and 4 but not zone 1 (Fig.…”

Section: Rncam a Novel Neuronal Cell Adhesion Molecule 26084mentioning

confidence: 92%

“…The RNCAM probe corresponded to the same 1.4-kbp region of RNCAM as was analyzed by Southern and Northern blot hybridization. OR probes used (M40, K20, L45, M50) and probes specific for G␣o and G␣i2 were as described previously (10,16,17). Images were processed using Adobe Photoshop 4.0.…”

Section: Methodsmentioning

confidence: 99%

Identification of a Novel Neural Cell Adhesion Molecule-related Gene with a Potential Role in Selective Axonal Projection

Alenius

Bohm

1997

Journal of Biological Chemistry

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We describe here the cloning of mouse complementary DNAs encoding a novel protein, Rb-8 neural cell adhesion molecule (RNCAM), with a predicted extracellular region of five immunoglobulin C2-type domains followed by two fibronectin type III domains. Alternative splicing is likely to generate two RNCAM isoforms, which are differently attached to the cell membrane. These structural features and overall sequence identity identify this protein as a novel member of a cell adhesion molecule subgroup together with vertebrate neural cell adhesion molecule, Aplysia cell adhesion molecule, and Drosophila fasciclin II. In insects, fasciclin II is present on a restricted subset of embryonic central nervous system axons where it controls selective axon fasciculation. Intriguingly, RNCAM likewise is expressed in subsets of olfactory and vomeronasal neurons with topographically defined axonal projections. The spatial expression RNCAM corresponds precisely to that of certain odorant receptor expression zones of the olfactory epithelium. These expression patterns thus render RNCAM the first described cell adhesion molecule with a potential regulatory role in formation of selective axonal projections important for olfactory sensory information coding.

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The chromosomal distribution of mouse odorant receptor genes.

Cited by 199 publications

References 35 publications

The human olfactory receptor gene family

The human olfactory receptor gene family

A feedback mechanism regulates monoallelic odorant receptor expression

Identification of a Novel Neural Cell Adhesion Molecule-related Gene with a Potential Role in Selective Axonal Projection

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