{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T20:39:05Z","timestamp":1770237545922,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ben and Esther Rosenbloom Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Experimental autoimmune thyroiditis is an important animal model for studying Hashimoto\u2019s thyroiditis. Our aim was to develop the model using CBA\/J-DR3 mice expressing human HLA-DR3, which is associated with autoimmune thyroiditis in humans, to better simulate human autoimmune thyroiditis. Such a humanized model can be used to test specific antigen therapies for autoimmune thyroiditis. Methods: CBA\/J-DR3 mice were produced by back-crossing B6-DR3 mice to the CBA\/J background. Female CBA\/J-DR3 mice were immunized with human thyroglobulin (Tg) in complete Freund\u2019s adjuvant on days 0 and 7. On day 21, mice were sacrificed, blood collected, spleen and thyroid harvested for analysis. Splenocytes were analyzed for T cell responses to Tg and its major T-cell epitope in human autoimmune thyroiditis, Tg.2098. Serum anti-thyroglobulin antibodies were measured by ELISA, and thyroid-stimulating hormone was measured using the Luminex assay. Thyroid histology and immunohistochemistry were examined. Results: Immunized CBA\/J-DR3 mice showed significant T cell proliferation in response to Tg (stimulation index 3.4 \u00b1 4.5) and Tg.2098 (1.5 \u00b1 0.7). Anti-thyroglobulin antibody levels were elevated in immunized mice when compared to control mice (2.05 \u00b1 0.75 vs. 0.15 \u00b1 0.06, p &lt; 0.0001). T cells demonstrated higher reactivity to thyroid antigens by enhanced production of pro-inflammatory cytokines. Thyroid immunohistochemistry revealed mild CD3-positive T-cell infiltration. Conclusions: This novel humanized CBA\/J-DR3 mouse model of Hashimoto\u2019s thyroiditis demonstrates key features of human autoimmune thyroiditis. The HLA-DR3 background and the immune response to Tg and Tg.2098 enhance translational relevance, making this a valuable model for studying thyroid disease pathogenesis and testing targeted immune-modifying therapies.<\/jats:p>","DOI":"10.3390\/genes17020170","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:48:08Z","timestamp":1770025688000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Using HLA-DR3-CBA\/J Humanized Mice to Develop a Novel Genetic Model for Autoimmune Thyroiditis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-5661","authenticated-orcid":false,"given":"Aizhan","family":"Kozhakhmetova","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Stefan-Lifshitz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8898-3440","authenticated-orcid":false,"given":"Olga","family":"Meshcheryakova","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaron","family":"Tomer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Weetman, A.P. 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