{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:20:28Z","timestamp":1787008828971,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations at the mouse microphthalmia locus (Mitf) affect the development of different cell types, including melanocytes, retinal pigment epithelial cells of the eye, and osteoclasts. The MITF protein is a member of the MYC supergene family of basic-helix-loop-helix-leucine-zipper (bHLHZip) transcription factors and is known to regulate the expression of cell-specific target genes by binding DNA as homodimer or as heterodimer with related proteins. The many mutations isolated at the locus have different effects on the phenotype and can be arranged in an allelic series in which the phenotypes range from near normal to white microphthalmic animals with osteopetrosis. Previous investigations have shown that certain combinations of Mitf alleles complement each other, resulting in a phenotype more normal than that of each homozygote alone. Here we analyze this interallelic complementation in detail and show that it is limited to one particular allele, MitfMi-white (MitfMi-wh), a mutation affecting the DNA-binding domain. Both loss- and gain-of-function mutations are complemented, as are other Mitf mutations affecting the DNA-binding domain. Furthermore, this behavior is not restricted to particular cell types: Both eye development and coat color phenotypes are complemented. Our analysis suggests that MitfMi-wh-associated interallelic complementation is due to the unique biochemical nature of this mutation.<\/jats:p>","DOI":"10.1093\/genetics\/163.1.267","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T01:12:01Z","timestamp":1619140321000},"page":"267-276","source":"Crossref","is-referenced-by-count":44,"title":["Interallelic Complementation at the Mouse\n                    <i>Mitf<\/i>\n                    Locus"],"prefix":"10.1093","volume":"163","author":[{"given":"Eir\u00edkur","family":"Steingr\u00edmsson","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, 101 Reykjav\u00edk, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Arnheiter","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, National Cancer Institute, NCI-FCRF, Frederick, Maryland 21702-1201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3n Hallsteinn","family":"Hallsson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, 101 Reykjav\u00edk, Iceland"},{"name":"Mouse Cancer Genetics Program, National Cancer Institute, NCI-FCRF, Frederick, Maryland 21702-1201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Lynn","family":"Lamoreux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal G","family":"Copeland","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy A","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,1,1]]},"reference":[{"key":"2022010518312262500_R1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/j.1460-2075.1994.tb06269.x","article-title":"Mutations in the Caenorhabditis elegans let-23 EGFR-like gene define elements important for cell-type specificity and function","volume":"13","author":"Aroian","year":"1994","journal-title":"EMBO J."},{"key":"2022010518312262500_R2","first-page":"7996","article-title":"Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator","volume":"14","author":"Bentley","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"2022010518312262500_R3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/BF03023302","article-title":"The relations of microphthalmia and white in the mouse","volume":"51","author":"Gr\u00fcneberg","year":"1953","journal-title":"J. Genet."},{"key":"2022010518312262500_R4","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/genetics\/155.1.291","article-title":"Genomic, transcriptional and mutational analysis of the mouse microphthalmia locus","volume":"155","author":"Hallsson","year":"2000","journal-title":"Genetics"},{"key":"2022010518312262500_R5","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1101\/gad.8.22.2770","article-title":"microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family","volume":"8","author":"Hemesath","year":"1994","journal-title":"Genes Dev."},{"key":"2022010518312262500_R6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0092-8674(93)90429-T","article-title":"Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein","volume":"74","author":"Hodgkinson","year":"1993","journal-title":"Cell"},{"key":"2022010518312262500_R7","first-page":"29","volume":"30","author":"Hollander","year":"1964","journal-title":"Mouse News Lett"},{"key":"2022010518312262500_R8","first-page":"189","article-title":"Complementary alleles at the mi-locus in the mouse","volume":"60","author":"Hollander","year":"1968","journal-title":"Genetics"},{"key":"2022010518312262500_R9","doi-asserted-by":"crossref","first-page":"20687","DOI":"10.1016\/S0021-9258(19)36830-9","article-title":"A helix-loop-helix transcription factor-like gene is located at the mi locus","volume":"268","author":"Hughes","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2022010518312262500_R10","first-page":"65","article-title":"Interallelic complementation of microphthalmia and white genes in mice","volume":"4","author":"Konyukhov","year":"1968","journal-title":"Genetika"},{"key":"2022010518312262500_R11","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/oxfordjournals.jhered.a111247","article-title":"The vit gene maps to the mi (Micropthalmia) locus of the laboratory mouse","volume":"83","author":"Lamoreux","year":"1992","journal-title":"J. Hered."},{"key":"2022010518312262500_R12","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/1523-1747.ep12524353","article-title":"A mouse model for vitiligo","volume":"87","author":"Lerner","year":"1986","journal-title":"J. Invest. Dermatol."},{"key":"2022010518312262500_R13","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S0168-9525(00)89143-X","article-title":"Insight into the microphthalmia gene","volume":"11","author":"Moore","year":"1995","journal-title":"Trends Genet."},{"key":"2022010518312262500_R14","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1182\/blood.V88.7.2488.bloodjournal8872488","article-title":"Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by the mi locus","volume":"88","author":"Morii","year":"1996","journal-title":"Blood"},{"key":"2022010518312262500_R15","doi-asserted-by":"crossref","first-page":"5798","DOI":"10.1073\/pnas.091479298","article-title":"Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression by the microphthalmia transcription factor family. Proc. Natl. Acad. Sci","volume":"98","author":"Motyckova","year":"2001","journal-title":"USA"},{"key":"2022010518312262500_R16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0925-4773(97)00188-3","article-title":"Mutations in microphthalmia, the mouse homolog of the human deafness gene MITF, affect neuroepithelial and neural crest-derived melanocytes differently","volume":"70","author":"Nakayama","year":"1998","journal-title":"Mech. Dev."},{"key":"2022010518312262500_R17","first-page":"M1","article-title":"Transvection and chromosomal trans-interaction effects. Biochim. Biophys","volume":"1424","author":"Pirrotta","year":"1999","journal-title":"Acta"},{"key":"2022010518312262500_R18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/genetics\/129.1.191","article-title":"Interallelic complementation among DER\/flb alleles: implications for the mechanisms of signal transduction by receptor-tyrosine kinases","volume":"129","author":"Raz","year":"1991","journal-title":"Genetics"},{"key":"2022010518312262500_R19","unstructured":"Schaible\n              R H\n            \n          , 1963 \u00a0Developmental genetics of spotting patterns in the mouse. Ph.D. Thesis, Iowa State University, Ames, IA."},{"key":"2022010518312262500_R20","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/ng1194-256","article-title":"Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences","volume":"8","author":"Steingr\u00edmsson","year":"1994","journal-title":"Nat. Genet."},{"key":"2022010518312262500_R21","doi-asserted-by":"crossref","first-page":"6280","DOI":"10.1002\/j.1460-2075.1996.tb01018.x","article-title":"The semidominant Mi-b mutation identifies a role for the HLH domain in DNA binding in addition to its role in protein dimerization","volume":"15","author":"Steingr\u00edmsson","year":"1996","journal-title":"EMBO J."},{"key":"2022010518312262500_R22","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1073\/pnas.072071099","article-title":"Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development. Proc. Natl. Acad. Sci","volume":"99","author":"Steingr\u00edmsson","year":"2002","journal-title":"USA"},{"key":"2022010518312262500_R23","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1128\/MCB.16.3.1203","article-title":"The recessive phenotype displayed by a dominant negative mirophthalmia-associated transcription factor mutant is a result of impaired nuclear localization potential","volume":"16","author":"Takebayashi","year":"1996","journal-title":"Mol. Cell. Biol."},{"key":"2022010518312262500_R24","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1017\/S0016672300022801","article-title":"A new allele of microphthalmia induced in the mouse: microphthalmia-defective iris (mi di)","volume":"46","author":"West","year":"1985","journal-title":"Genet. Res."},{"key":"2022010518312262500_R25","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1017\/S001667230003487X","article-title":"Mi-spotted: a mutation in the mouse","volume":"5","author":"Wolfe","year":"1964","journal-title":"Genet. Res."},{"key":"2022010518312262500_R26","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1093\/hmg\/8.8.1431","article-title":"An L1 element intronic insertion in the black-eyed white (Mitf mi-bw) gene: the loss of a single Mitf isoform responsible for the pigmentary defect and inner ear deafness","volume":"8","author":"Yajima","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"2022010518312262500_R27","first-page":"23","article-title":"Molecular cloning of a cDNA encoding a human TFEC isoform, a newly identified transcriptional regulator. Biochim. Biophys","volume":"1353","author":"Yasumoto","year":"1997","journal-title":"Acta"},{"key":"2022010518312262500_R28","first-page":"8058","article-title":"Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene","volume":"14","author":"Yasumoto","year":"1994","journal-title":"Mol. Cell. Biol."}],"container-title":["Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/163\/1\/267\/42052101\/genetics0267.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/163\/1\/267\/42052101\/genetics0267.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T13:39:58Z","timestamp":1641389998000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/genetics\/article\/163\/1\/267\/6052877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,1]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2003,1,1]]},"published-print":{"date-parts":[[2003,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/genetics\/163.1.267","relation":{},"ISSN":["1943-2631"],"issn-type":[{"value":"1943-2631","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,1,1]]},"published":{"date-parts":[[2003,1,1]]}}}