{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:56:04Z","timestamp":1791143764003,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,11,12]]},"abstract":"<jats:p>\n                    Deafness in spontaneously occurring mouse mutants is often associated with defects in cochlea sensory hair cells, opening an avenue to systematically identify genes critical for hair cell structure and function. The classical semidominant mouse mutant varitint-waddler (\n                    <jats:italic>Va<\/jats:italic>\n                    ) exhibits early-onset hearing loss, vestibular defects, pigmentation abnormalities, and perinatal lethality. A second allele,\n                    <jats:italic>\n                      Va\n                      <jats:sup>J<\/jats:sup>\n                    <\/jats:italic>\n                    , which arose in a cross segregating for\n                    <jats:italic>Va<\/jats:italic>\n                    , shows a less severe phenotype. By using a positional cloning strategy, we identify two additional members of the mucolipin gene family (\n                    <jats:italic>Mcoln2<\/jats:italic>\n                    and\n                    <jats:italic>Mcoln3<\/jats:italic>\n                    ) in the 350-kb\n                    <jats:italic>\n                      Va\n                      <jats:sup>J<\/jats:sup>\n                    <\/jats:italic>\n                    minimal interval and provide evidence for\n                    <jats:italic>Mcoln3<\/jats:italic>\n                    as the gene mutated in varitint-waddler.\n                    <jats:italic>Mcoln3<\/jats:italic>\n                    encodes a putative six-transmembrane-domain protein with sequence and motif similarities to the family of nonselective transient-receptor-potential (TRP) ion channels. In the\n                    <jats:italic>Va<\/jats:italic>\n                    allele an Ala419Pro substitution occurs in the fifth transmembrane domain of\n                    <jats:italic>Mcoln3<\/jats:italic>\n                    , and in\n                    <jats:italic>\n                      Va\n                      <jats:sup>J<\/jats:sup>\n                    <\/jats:italic>\n                    , a second sequence alteration (Ile362Thr) occurring in cis partially rescues the\n                    <jats:italic>Va<\/jats:italic>\n                    allele. Mcoln3 localizes to cytoplasmic compartments of hair cells and plasma membrane of stereocilia. Hair cell defects are apparent by embryonic day 17.5, assigning\n                    <jats:italic>Mcoln3<\/jats:italic>\n                    an essential role during early hair cell maturation. Our data suggest that Mcoln3 is involved in ion homeostasis and acts cell-autonomously. Hence, we identify a molecular link between hair cell physiology and melanocyte function. Last,\n                    <jats:italic>MCOLN2<\/jats:italic>\n                    and\n                    <jats:italic>MCOLN3<\/jats:italic>\n                    are candidate genes for hereditary and\/or sporadic forms of neurosensory disorders in humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.222425399","type":"journal-article","created":{"date-parts":[[2002,11,12]],"date-time":"2002-11-12T13:44:20Z","timestamp":1037108660000},"page":"14994-14999","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":203,"title":["Mutations in\n                    <i>Mcoln3<\/i>\n                    associated with deafness and pigmentation defects in varitint-waddler (\n                    <i>Va<\/i>\n                    ) mice"],"prefix":"10.1073","volume":"99","author":[{"given":"Federica","family":"Di Palma","sequence":"first","affiliation":[{"name":"Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850; Section on Structural Cell Biology, Laboratory of Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 50 Convent Drive, Bethesda, MD 20892; and Department of Molecular Biology, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna A.","family":"Belyantseva","sequence":"additional","affiliation":[{"name":"Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850; Section on Structural Cell Biology, Laboratory of Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 50 Convent Drive, Bethesda, MD 20892; and Department of Molecular Biology, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850; Section on Structural Cell Biology, Laboratory of Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 50 Convent Drive, Bethesda, MD 20892; and Department of Molecular Biology, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Vogt","sequence":"additional","affiliation":[{"name":"Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850; Section on Structural Cell Biology, Laboratory of Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 50 Convent Drive, Bethesda, MD 20892; and Department of Molecular Biology, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bechara","family":"Kachar","sequence":"additional","affiliation":[{"name":"Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850; Section on Structural Cell Biology, Laboratory of Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 50 Convent Drive, Bethesda, MD 20892; and Department of Molecular Biology, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Noben-Trauth","sequence":"additional","affiliation":[{"name":"Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850; Section on Structural Cell Biology, Laboratory of Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 50 Convent Drive, Bethesda, MD 20892; and Department of Molecular Biology, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,10,25]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/84758"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90020-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/335088a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/347667a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90303-V"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90429-T"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1994.tb00015.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(94)00331-G"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a105514"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a108252"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02985081"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(98)00107-5"},{"key":"e_1_3_3_13_2","unstructured":"Kim H. 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