{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T05:44:03Z","timestamp":1792907043607,"version":"4.5.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["F32 DK134148"],"award-info":[{"award-number":["F32 DK134148"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK128898"],"award-info":[{"award-number":["R01 DK128898"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["24CDA1269864"],"award-info":[{"award-number":["24CDA1269864"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U54 HL170326"],"award-info":[{"award-number":["U54 HL170326"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Four Core Genotypes (FCG) mouse model has become a valuable model to study the mechanistic basis for biological sex differences. This model allows discrimination between influences of gonadal sex (ovaries or testes) from those associated with genetic sex (presence of XX or XY chromosome complement). FCG mice have illuminated distinct effects of gonadal and chromosomal sex on traits ranging from brain structure and behavior to vulnerability to obesity, atherosclerosis, multiple sclerosis, Alzheimer\u2019s and other diseases. A recent study determined that the Y<jats:sup><jats:italic>Sry<\/jats:italic>\u2212<\/jats:sup> chromosome used in a specific line of C57BL\/6J FCG mice harbors nine genes that have been duplicated from the X chromosome. This report raised concern that scores of publications that previously used the FCG model may therefore be flawed, but did not provide details regarding how studies can be evaluated for potential impact (or lack of impact) of the translocation. Here we (1) provide a practical description of the genetic translocation for researchers using the FCG model, (2) document that a majority of the studies cited in the recent report are unlikely to be affected by the translocation, (3) provide a scheme for interpreting data from studies with FCG mice harboring the Y<jats:sup><jats:italic>Sry<\/jats:italic>\u2212<\/jats:sup> translocation, and (4) delineate expression levels of the nine translocated genes across tissue\/cell types as a filter for evaluating their potential involvement in specific phenotypes.<\/jats:p>","DOI":"10.1186\/s13293-024-00665-5","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T19:02:39Z","timestamp":1730401359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation"],"prefix":"10.1186","volume":"15","author":[{"given":"Carrie B.","family":"Wiese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Reue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"665_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13293-024-00610-6","volume":"15","author":"A Gompers","year":"2024","unstructured":"Gompers A, Oliver MT, Maney DL. Training in the implementation of sex and gender research policies: an evaluation of publicly available online courses. Biol Sex Differ. 2024;15:32.","journal-title":"Biol Sex Differ"},{"key":"665_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2020.09.021","volume":"119","author":"AP Arnold","year":"2020","unstructured":"Arnold AP. Four Core Genotypes and XY* mouse models: update on impact on SABV research. Neurosci Biobehav Rev. 2020;119:1\u20138.","journal-title":"Neurosci Biobehav Rev"},{"key":"665_CR3","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.tem.2023.07.003","volume":"34","author":"CB Wiese","year":"2023","unstructured":"Wiese CB, Avetisyan R, Reue K. The impact of chromosomal sex on cardiometabolic health and disease. Trends Endocrinol Metab. 2023;34:652\u201365.","journal-title":"Trends Endocrinol Metab"},{"key":"665_CR4","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1161\/CIRCRESAHA.122.320259","volume":"130","author":"K Reue","year":"2022","unstructured":"Reue K, Wiese CB. Illuminating the mechanisms underlying sex differences in cardiovascular disease. Circ Res. 2022;130:1747\u201362.","journal-title":"Circ Res"},{"key":"665_CR5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13293-016-0115-5","volume":"7","author":"PS Burgoyne","year":"2016","unstructured":"Burgoyne PS, Arnold AP. A primer on the use of mouse models for identifying direct sex chromosome effects that cause sex differences in non-gonadal tissues. Biol Sex Differ. 2016;7:68.","journal-title":"Biol Sex Differ"},{"key":"665_CR6","doi-asserted-by":"publisher","first-page":"8814","DOI":"10.1038\/s41467-024-52640-8","volume":"15","author":"J Panten","year":"2024","unstructured":"Panten J, Del Prete S, Cleland JP, Saunders LM, van Riet J, Schneider A, et al. Four-Core Genotypes mice harbour a 3.2\u00a0MB X\u2013Y translocation that perturbs Tlr7 dosage. Nat Commun. 2024;15:8814.","journal-title":"Nat Commun"},{"key":"665_CR7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005079","volume":"11","author":"JB Berletch","year":"2015","unstructured":"Berletch JB, Ma W, Yang F, Shendure J, Noble WS, Disteche CM, et al. Escape from X inactivation varies in mouse tissues. PLoS Genet. 2015;11: e1005079.","journal-title":"PLoS Genet"},{"key":"665_CR8","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1534\/genetics.116.197988","volume":"206","author":"AP Morgan","year":"2017","unstructured":"Morgan AP, Gatti DM, Najarian ML, Keane TM, Galante RJ, Pack AI, et al. Structural variation shapes the landscape of recombination in mouse. Genetics. 2017;206:603\u201319.","journal-title":"Genetics"},{"key":"665_CR9","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1016\/j.cmet.2017.04.033","volume":"25","author":"F Mauvais-Jarvis","year":"2017","unstructured":"Mauvais-Jarvis F, Arnold AP, Reue K. A Guide for the design of pre-clinical studies on sex differences in metabolism. Cell Metab. 2017;25:1216\u201330.","journal-title":"Cell Metab"},{"key":"665_CR10","doi-asserted-by":"publisher","first-page":"eaaz5677","DOI":"10.1126\/scitranslmed.aaz5677","volume":"12","author":"EJ Davis","year":"2020","unstructured":"Davis EJ, Broestl L, Williams G, Garay BI, Lobach I, Devidze N, et al. A second X chromosome contributes to resilience in a mouse model of Alzheimer\u2019s disease. Sci Transl Med. 2020;12:eaaz5677.","journal-title":"Sci Transl Med"},{"key":"665_CR11","doi-asserted-by":"publisher","first-page":"5688","DOI":"10.1172\/JCI140223","volume":"130","author":"JC Link","year":"2020","unstructured":"Link JC, Wiese CB, Chen X, Avetisyan R, Ronquillo E, Ma F, et al. X chromosome dosage of histone demethylase KDM5C determines sex differences in adiposity. 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