A Mendelian Trait for Olfactory Sensitivity Affects Odor Experience and Food Selection

Jaeger, Sara R.; McRae, Jeremy F.; Bava, Christina M.; Beresford, Michelle K.; Hunter, Denise C.; Jia, Yilin; Chheang, Sok L.; Jin, David; Peng, Mei; Gamble, Joanna; Atkinson, Kelly R.; Axten, Lauren G.; Paisley, Amy G.; Tooman, Leah; Pineau, Bénédicte; Rouse, Simon A.; Newcomb, Richard D.

doi:10.1016/j.cub.2013.07.030

Cited by 179 publications

(131 citation statements)

References 30 publications

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“…However, to our knowledge, this was the first case in which a single OR deletion affected the perception of the cognate ligand in mice. In humans, there are some cases in which genetic variation in a single receptor has a large influence on the intensity, sensitivity, or preference to the cognate odorant (Keller et al, 2007;Menashe et al, 2007;McRae et al, 2012;Jaeger et al, 2013;. These account for specific anosmia or hyperosmia for a particular odor.…”

Section: Discussionmentioning

confidence: 99%

Ligand Specificity and Evolution of Mammalian Musk Odor Receptors: Effect of Single Receptor Deletion on Odor Detection

et al. 2016

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Musk odors have been used widely for fragrance and medicine for Ͼ2000 years because of their fascinating scent and physiological effects. Therefore, fragrance manufacturers have been eager to develop high-quality musk compounds that are safe and easily synthesized. We recently identified muscone-responsive olfactory receptors (ORs) MOR215-1 and OR5AN1 in mice and humans, respectively (Shirasu et al., 2014). In this study, we identified musk ORs that are evolutionarily closely related to MOR215-1 or OR5AN1 in various primates and investigated structure-activity relationships for various musk odorants and related compounds. We found that each species has one or two functional musk ORs that exhibit specific ligand spectra to musk compounds. Some of them, including the human OR5AN1, responded to nitro musks with chemical properties distinct from muscone. The ligand specificity of OR5AN1 reflects the perception of musk odors in humans. Genetic deletion of MOR215-1 in mice resulted in drastic reduction of sensitivity to muscone, suggesting that MOR215-1 plays a critical role in muscone perception. Therefore, the current study reveals a clear link between the identified OR and muscone perception. Moreover, the strategy established for screening ligands for the muscone OR may facilitate the development of novel and commercially useful musk odors.

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Section: Discussionmentioning

confidence: 99%

Ligand Specificity and Evolution of Mammalian Musk Odor Receptors: Effect of Single Receptor Deletion on Odor Detection

et al. 2016

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“…Odorant identity is encoded by olfactory receptor activation patterns, but receptor activation patterns, including which receptors are activated and to what degree, are known for fewer than 6% of human olfactory receptors [1][2][3][4][5][6][7][8][9][10][11] . Efforts to characterize olfactory receptors have been limited by their labor-intensive methods or applicability to only a subset of the olfactory receptor family 17,23,24,33,34 .…”

Section: Discussionmentioning

confidence: 99%

“…Matching ligands to ORs is critical for understanding the olfactory code and essential for building viable models of olfaction. Due to difficulties expressing ORs in heterologous systems as well as the large number of both odorants and ORs, this data has been largely absent from the field; indeed, fewer than 6% of human ORs have a published ligand [1][2][3][4][5][6][7][8][9][10][11] . This protocol describes the use of a luciferase assay to characterize odorant/OR interactions.…”

Section: Introductionmentioning

confidence: 99%

“…When candidate olfactory odorant/OR pairs are identified via these screens, interaction can be confirmed by conducting a dose response experiment examining the response of the OR to increasing concentrations of odorant. Dose response curves can also assess how genetic variation in an OR affects in vitro odorant response 8,9,11,35 , and these studies can be extended to interspecific OR variation, allowing for the examination of receptor evolution across species and causal mutations in evolution 36,37 , Finally, this assay can be used to screen for odor antagonists that are able to antagonize OR response to a particular odorant for a known odorant/receptor pair 38,39 . In summary, this high-throughput luciferase assay is applicable to a range of studies that will help characterize OR activation patterns and provide a better understanding of odor coding in the olfactory system.…”

Section: Introductionmentioning

confidence: 99%

“…Odorant ligands have been published for fewer than 6% of human receptors [1][2][3][4][5][6][7][8][9][10][11] . This lack of data is due in part to difficulties functionally expressing these receptors in heterologous systems.…”

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confidence: 99%

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High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity

Trimmer

Snyder

Mainland

2014

JoVE

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Odorants create unique and overlapping patterns of olfactory receptor activation, allowing a family of approximately 1,000 murine and 400 human receptors to recognize thousands of odorants. Odorant ligands have been published for fewer than 6% of human receptors [1][2][3][4][5][6][7][8][9][10][11] . This lack of data is due in part to difficulties functionally expressing these receptors in heterologous systems. Here, we describe a method for expressing the majority of the olfactory receptor family in Hana3A cells, followed by high-throughput assessment of olfactory receptor activation using a luciferase reporter assay. This assay can be used to (1) screen panels of odorants against panels of olfactory receptors; (2) confirm odorant/ receptor interaction via dose response curves; and (3) compare receptor activation levels among receptor variants. In our sample data, 328 olfactory receptors were screened against 26 odorants. Odorant/receptor pairs with varying response scores were selected and tested in dose response. These data indicate that a screen is an effective method to enrich for odorant/receptor pairs that will pass a dose response experiment, i.e. receptors that have a bona fide response to an odorant. Therefore, this high-throughput luciferase assay is an effective method to characterize olfactory receptors-an essential step toward a model of odor coding in the mammalian olfactory system. Video LinkThe video component of this article can be found at

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Olfactory Receptor Genes: Evolution

Niimura

2014

Encyclopedia of Life Sciences

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Many mammal genomes have approximately 1000 genes encoding olfactory receptors (ORs), and OR genes constitute the largest multigene family in mammals. Comparisons among the OR gene repertoires in a broad range of species demonstrates that gene duplication and pseudogenization cause frequent gene gain and loss in this family, causing drastic evolutionary changes in the number of genes depending on species' ecological niches and other sensory modalities. For example, higher primates are equipped with a well‐developed visual system, and they have a reduced OR gene repertoires relative to mammals with lesser visual systems. Additionally, aquatic and terrestrial vertebrates retain different sets of OR genes, and these sets reflect the capacity to detect water‐soluble and airborne odorants, respectively. The origin of vertebrate OR genes can be traced back to the common ancestor of chordates, but insects and nematodes each use a distinct family of genes to encode chemoreceptors; therefore, multiple distinct chemoreceptor gene families emerged independently during animal evolution. Key Concepts: Olfactory receptor (OR) genes are the largest multigene family in mammals. OR gene repertoires changed dynamically during mammalian evolution and these changes depended on each species' ecological niches and other sensory modalities. Distinct chemoreceptor gene families have emerged independently multiple times during animal evolution. Comparative evolutionary analysis of OR genes provides insights into the interactions between genomes and environments.

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A Mendelian Trait for Olfactory Sensitivity Affects Odor Experience and Food Selection

Cited by 179 publications

References 30 publications

Ligand Specificity and Evolution of Mammalian Musk Odor Receptors: Effect of Single Receptor Deletion on Odor Detection

Ligand Specificity and Evolution of Mammalian Musk Odor Receptors: Effect of Single Receptor Deletion on Odor Detection

High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity

Olfactory Receptor Genes: Evolution

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