{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:53:54Z","timestamp":1783486434316,"version":"3.55.0"},"reference-count":51,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans.<\/jats:p>","DOI":"10.1210\/en.2014-1388","type":"journal-article","created":{"date-parts":[[2014,7,22]],"date-time":"2014-07-22T17:27:33Z","timestamp":1406050053000},"page":"4094-4103","source":"Crossref","is-referenced-by-count":5,"title":["Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice"],"prefix":"10.1210","volume":"155","author":[{"given":"Sandra M.","family":"McLachlan","sequence":"first","affiliation":[{"name":"Thyroid Autoimmune Disease Unit (S.M.M., H.A., B.B., J.M., B.R.), Cedars-Sinai Research Institute and UCLA School of Medicine, Los Angeles, California 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Aliesky","sequence":"first","affiliation":[{"name":"Thyroid Autoimmune Disease Unit (S.M.M., H.A., B.B., J.M., B.R.), Cedars-Sinai Research Institute and UCLA School of Medicine, Los Angeles, California 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Banuelos","sequence":"first","affiliation":[{"name":"Thyroid Autoimmune Disease Unit (S.M.M., H.A., B.B., J.M., B.R.), Cedars-Sinai Research Institute and UCLA School of Medicine, Los Angeles, California 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Magana","sequence":"first","affiliation":[{"name":"Thyroid Autoimmune Disease Unit (S.M.M., H.A., B.B., J.M., B.R.), Cedars-Sinai Research Institute and UCLA School of Medicine, Los Angeles, California 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology (R.W.W.), University of Tennessee Health-Science Center, Memphis, Tennessee 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil","family":"Rapoport","sequence":"first","affiliation":[{"name":"Thyroid Autoimmune Disease Unit (S.M.M., H.A., B.B., J.M., B.R.), Cedars-Sinai Research Institute and UCLA School of Medicine, Los Angeles, California 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612123800000_B1","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1210\/en.2006-0160","article-title":"Probing the genetic basis for thyrotropin receptor antibodies and hyperthyroidism in immunized CXB recombinant inbred mice","volume":"147","author":"Aliesky","year":"2006","journal-title":"Endocrinology"},{"key":"2020071612123800000_B2","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1210\/en.2007-1517","article-title":"Shared and unique susceptibility genes in a mouse model of Graves' disease determined in BXH and CXB recombinant inbred mice","volume":"149","author":"McLachlan","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612123800000_B3","doi-asserted-by":"crossref","first-page":"e21378","DOI":"10.1371\/journal.pone.0021378","article-title":"Exceptional hyperthyroidism and a role for both major histocompatibility class I and class II genes in a murine model of Graves' disease","volume":"6","author":"McLachlan","year":"2011","journal-title":"PLoS One"},{"key":"2020071612123800000_B4","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1172\/JCI200317069","article-title":"The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim","volume":"111","author":"Chen","year":"2003","journal-title":"J Clin Invest"},{"key":"2020071612123800000_B5","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/gene.2010.8","article-title":"Immunoglobulin heavy chain variable region genes contribute to the induction of thyroid-stimulating antibodies in recombinant inbred mice","volume":"11","author":"Rapoport","year":"2010","journal-title":"Genes Immun"},{"key":"2020071612123800000_B6","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1210\/en.2010-1138","article-title":"Distinct genetic signatures for variability in total and free serum thyroxine levels in four sets of recombinant inbred mice","volume":"152","author":"McLachlan","year":"2011","journal-title":"Endocrinology"},{"key":"2020071612123800000_B7","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1089\/thy.2012.0338","article-title":"Genetic linkages for thyroxine released in response to TSH stimulation in three sets of recombinant inbred mice provide evidence for shared and novel genes controlling thyroid function","volume":"23","author":"Hamidi","year":"2013","journal-title":"Thyroid"},{"key":"2020071612123800000_B8","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/00007890-197103000-00013","article-title":"Recombinant-inbred strains. 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