{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:53:53Z","timestamp":1792785233626,"version":"4.5.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"39","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Key Research & Development Program of China","award":["2023YFC2705902"],"award-info":[{"award-number":["2023YFC2705902"]}]},{"name":"National Natural Science Foundation of China","award":["32470880"],"award-info":[{"award-number":["32470880"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20210324120205015"],"award-info":[{"award-number":["JCYJ20210324120205015"]}]},{"name":"Zhangjiakou City Key R&D Plan Project","award":["No.2322088D"],"award-info":[{"award-number":["No.2322088D"]}]},{"name":"Key Clinical Projects of Peking University Third Hospital","award":["BYSYZD2023033"],"award-info":[{"award-number":["BYSYZD2023033"]}],"id":[{"id":"https:\/\/ror.org\/04wwqze12","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Natural science project of Hebei North University","award":["No.XJ2024035"],"award-info":[{"award-number":["No.XJ2024035"]}],"id":[{"id":"https:\/\/ror.org\/03hqwnx39","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Peking University Medicine Sailing Program for Young Scholars& Scientific & Technological Innovation","award":["BMU2025YFJHPY035"],"award-info":[{"award-number":["BMU2025YFJHPY035"]}],"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,30]]},"abstract":"<jats:p>\n                    Targeting exogenous gene integrations in animals often exhibits low efficiency, limiting the development of gene knock-in models. Theoretically, by screening founder generation individuals based on the cell phenotypes resulting from gene knock-ins and leveraging the high fecundity of animals, heritable descendants with targeted knock-ins can be efficiently generated. Therefore, we utilized the high fecundity of\n                    <jats:italic toggle=\"yes\">Xenopus tropicalis<\/jats:italic>\n                    and easily observable pigment phenotypes to construct a\n                    <jats:italic toggle=\"yes\">\n                      BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                    <\/jats:italic>\n                    -targeted\n                    <jats:italic toggle=\"yes\">mitf<\/jats:italic>\n                    locus knock-in model. Results indicated that this approach enabled efficient generation of\n                    <jats:italic toggle=\"yes\">\n                      BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                    <\/jats:italic>\n                    knock-in\n                    <jats:italic toggle=\"yes\">X. tropicalis<\/jats:italic>\n                    and produced a versatile frog model. The\n                    <jats:italic toggle=\"yes\">\n                      BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                    <\/jats:italic>\n                    knock-in induced the transdifferentiation of RPE cells into retinal cells, resulting in a symmetric retinal structure in the eyes of these frogs. The transformation of RPE cells ultimately leads to these frogs becoming eyeless frogs, which serve as a tool for retinal regeneration research. Additionally, in eyeless frogs the\n                    <jats:italic toggle=\"yes\">\n                      BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                    <\/jats:italic>\n                    knock-in led to the abnormal proliferation of both melanocytes and xanthophores into melanocytic and xanthocytic nevi respectively. Consequently, eyeless frogs provide a model for studying abnormal pigment cell proliferation, offering a platform for investigating pigment cell nevus formation. Furthermore, the\n                    <jats:italic toggle=\"yes\">cdkn2b<\/jats:italic>\n                    -knockout eyeless frogs serve as a valuable xanthophoroma model for tumor biology research. Overall, the\n                    <jats:italic toggle=\"yes\">\n                      BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                    <\/jats:italic>\n                    -targeted knock-in\n                    <jats:italic toggle=\"yes\">X. tropicalis<\/jats:italic>\n                    not only represents a strategy for constructing gene knock-in animal models but also serves as a versatile tool for research in retinal regeneration and tumor biology.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2426981122","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T15:51:10Z","timestamp":1758901870000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Versatile\n                    <i>Xenopus tropicalis<\/i>\n                    model with targeted integration of human\n                    <i>\n                      BRAF\n                      <sup>V600E<\/sup>\n                    <\/i>"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9863-4735","authenticated-orcid":false,"given":"Rensen","family":"Ran","sequence":"first","affiliation":[{"name":"State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Department of Biology, School of Life Sciences, Southern University of Science and Technology","place":["Shenzhen, China"]},{"name":"National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Life Sciences, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The second affiliated hospital of Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-7781","authenticated-orcid":false,"given":"Shuai","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Center of Cardiometabolic Diseases, Guangdong Medical University","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1009-6416","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hebei North University","place":["Zhangjiakou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenpeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hebei North University","place":["Zhangjiakou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, School of Health Care, Changchun Vocational College of Health","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4933-113X","authenticated-orcid":false,"given":"Yonglong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Life Sciences, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0334-6467","authenticated-orcid":false,"given":"Jing","family":"Hang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7274-6034","authenticated-orcid":false,"given":"Weizheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Systems Biology and Gene Regulation, Central Laboratory, The First Affiliated Hospital of Hebei North University","place":["Zhangjiakou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.123.000967"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-023-00568-4"},{"key":"e_1_3_5_3_2","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041736","article-title":"The evolution of mouse models of cancer: Past, present, and future","volume":"15","author":"Abate-Shen C.","year":"2024","unstructured":"C. Abate-Shen, K. Politi, The evolution of mouse models of cancer: Past, present, and future. Cold Spring Harb. Perspect. Med. 15, a041736 (2024). 10.1101\/cshperspect.a041736.","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.042"},{"key":"e_1_3_5_5_2","doi-asserted-by":"crossref","unstructured":"Y. Liu J. Kong G. Liu Z. Li Y. Xiao Precise gene knock-in tools with minimized risk of DSBs: A trend for gene manipulation. Adv. Sci. 11 e2401797 (2024).","DOI":"10.1002\/advs.202401797"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3950"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.add8643"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1183670"},{"key":"e_1_3_5_9_2","first-page":"225","article-title":"Engineering Xenopus embryos for phenotypic drug discovery screening","volume":"69","author":"Stefan S.","year":"2014","unstructured":"S. Stefan, G. Mazhar, B. Andr\u00e9, Engineering Xenopus embryos for phenotypic drug discovery screening. Adv. Drug Deliv. Rev. 69, 225\u2013246 (2014).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"e_1_3_5_10_2","first-page":"505","article-title":"Xenopus research: Metamorphosed by genetics and genomics","volume":"27","author":"Richard H.","year":"2011","unstructured":"H. Richard, G. Robert, Xenopus research: Metamorphosed by genetics and genomics. Trends Genet. 27, 505\u2013515 (2011).","journal-title":"Trends Genet."},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01800-4"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04979-5"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47093-y"},{"key":"e_1_3_5_14_2","first-page":"12","article-title":"A brief history of Xenopus in biology","volume":"1","author":"Edward D. R.","year":"2021","unstructured":"D. R. Edward, G. John, A brief history of Xenopus in biology. Cold Spring Harb. Protoc. 1, 12 (2021).","journal-title":"Cold Spring Harb. Protoc."},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.050754"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-273425"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.099853"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2024.115295"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.01.011"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15546-9"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering10060673"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13301"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-05967-3"},{"key":"e_1_3_5_24_2","first-page":"1","article-title":"Decoding the molecular mechanisms of BRAF V600E-induced nevi formation","volume":"37","author":"Zheng L. W.","year":"2024","unstructured":"L. W. Zheng, L. Y. Xuan, X. D. Dan, J. W. Jie, R. R. Sen, Decoding the molecular mechanisms of BRAF V600E-induced nevi formation. Biomed. Environ. Sci. 37, 1\u201311 (2024).","journal-title":"Biomed. Environ. Sci."},{"key":"e_1_3_5_25_2","article-title":"Xenopus as a model system for studying pigmentation and pigmentary disorders","volume":"38","author":"Joudi E. M.","year":"2024","unstructured":"E. M. Joudi , Xenopus as a model system for studying pigmentation and pigmentary disorders. Pigment Cell Melanoma Res. 38, e13178 (2024). 10.1111\/pcmr.13178.","journal-title":"Pigment Cell Melanoma Res."},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.97475"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.324657.119"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00852-0"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-2138"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00215-6"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00194-4"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2013.10.003"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-025-02168-0"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0736"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.09.003"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2007.00911.x"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40139-017-0127-9"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1993.12.667"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199708)209:4<387::AID-AJA6>3.0.CO;2-E"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(95)00255-7"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.24.5051"},{"key":"e_1_3_5_42_2","first-page":"1981","article-title":"Cellular and molecular triggers of retinal regeneration in amphibians","volume":"13","author":"Yuliya M.","year":"2023","unstructured":"M. Yuliya, G. Eleonora, Cellular and molecular triggers of retinal regeneration in amphibians. Life (Basel) 13, 1981 (2023).","journal-title":"Life (Basel)"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1987.tb00531.x"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2022.07.016"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.05.014"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.314"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.526"},{"key":"e_1_3_5_48_2","article-title":"BRAF\/MAPK and GSK3 signaling converges to control MITF nuclear export","volume":"115","author":"Kao Chin N.","year":"2018","unstructured":"N. Kao Chin , BRAF\/MAPK and GSK3 signaling converges to control MITF nuclear export. Proc. Natl. Acad. Sci. U.S.A. 115, E8668 (2018).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.06.002"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01175-5"},{"key":"e_1_3_5_51_2","doi-asserted-by":"crossref","unstructured":"H. Yi Melanin deposition and key molecular features in Xenopus tropicalis oocytes. BMC Biol. 23 62 (2025).","DOI":"10.1186\/s12915-025-02168-0"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.06629.x"}],"updated-by":[{"DOI":"10.1073\/pnas.2634147123","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2426981122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:17:59Z","timestamp":1791832679000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2426981122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":52,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2025,9,30]]}},"alternative-id":["10.1073\/pnas.2426981122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2426981122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]},"assertion":[{"value":"2024-12-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2426981122"}}