{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:19:58Z","timestamp":1790929198042,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"40","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,10,2]]},"abstract":"<jats:p>\n                    Cilia regulate diverse functions such as motility, fluid balance, and sensory perception. The cilia of olfactory sensory neurons (OSNs) compartmentalize the signaling proteins necessary for odor detection; however, little is known regarding the mechanisms of protein sorting\/entry into olfactory cilia. Nephrocystins are a family of ciliary proteins likely involved in cargo sorting during transport from the basal body to the ciliary axoneme. In humans, loss-of-function of the cilia\u2013centrosomal protein CEP290\/NPHP6 is associated with Joubert and Meckel syndromes, whereas hypomorphic mutations result in Leber congenital amaurosis (LCA), a form of early-onset retinal dystrophy. Here, we report that CEP290\u2013LCA patients exhibit severely abnormal olfactory function. In a mouse model with hypomorphic mutations in CEP290 [retinal dystrophy-16 mice (\n                    <jats:italic>rd16<\/jats:italic>\n                    )], electro-olfactogram recordings revealed an anosmic phenotype analogous to that of CEP290\u2013LCA patients. Despite the loss of olfactory function, cilia of OSNs remained intact in the\n                    <jats:italic>rd16<\/jats:italic>\n                    mice. As in wild type, CEP290 localized to dendritic knobs of\n                    <jats:italic>rd16<\/jats:italic>\n                    OSNs, where it was in complex with ciliary transport proteins and the olfactory G proteins G\n                    <jats:sub>olf<\/jats:sub>\n                    and G\u03b3\n                    <jats:sub>13<\/jats:sub>\n                    . Interestingly, we observed defective ciliary localization of G\n                    <jats:sub>olf<\/jats:sub>\n                    and G\u03b3\n                    <jats:sub>13<\/jats:sub>\n                    but not of G protein-coupled odorant receptors or other components of the odorant signaling pathway in the\n                    <jats:italic>rd16<\/jats:italic>\n                    OSNs. Our data implicate distinct mechanisms for ciliary transport of olfactory signaling proteins, with CEP290 being a key mediator involved in G protein trafficking. The assessment of olfactory function can, therefore, serve as a useful diagnostic tool for genetic screening of certain syndromic ciliary diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0704140104","type":"journal-article","created":{"date-parts":[[2007,9,26]],"date-time":"2007-09-26T20:59:10Z","timestamp":1190840350000},"page":"15917-15922","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":149,"title":["Hypomorphic CEP290\/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons"],"prefix":"10.1073","volume":"104","author":[{"given":"Dyke P.","family":"McEwen","sequence":"first","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert K.","family":"Koenekoop","sequence":"additional","affiliation":[{"name":"McGill Ocular Genetics Laboratory, Montreal Children's Hospital Research Institute, McGill University Health Centre, Montreal, QC, Canada H3H 1P3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemant","family":"Khanna","sequence":"additional","affiliation":[{"name":"Ophthalmology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Lopez","sequence":"additional","affiliation":[{"name":"McGill Ocular Genetics Laboratory, Montreal Children's Hospital Research Institute, McGill University Health Centre, Montreal, QC, Canada H3H 1P3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Swaroop","sequence":"additional","affiliation":[{"name":"Ophthalmology, and"},{"name":"Human Genetics, University of Michigan, Ann Arbor, MI 48105; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Martens","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,10,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm952"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.7.080505.115610"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.06.009"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.69.040705.141236"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90418-X"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90287-N"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1418"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01765-3"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80435-3"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80200-7"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00060-X"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.111401.091318"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1727"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505827200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/519494"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005121351"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600885"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02665"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi061"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2003121025"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1786"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1805"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl107"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/507318"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9485"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30512"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2006.00516.x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.7.1035"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi129"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600697103"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4595-04.2005"},{"key":"e_1_3_4_32_2","author":"Cideciyan AV","year":"2007","unstructured":"AV Cideciyan, TS Aleman, SG Jacobson, H Khanna, A Sumaroka, GK Aguirre, SB Schwartz, EA Windsor, S He, B Chang, et al. 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