{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T05:14:05Z","timestamp":1765084445498,"version":"3.46.0"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["075-15-2025-475"],"award-info":[{"award-number":["075-15-2025-475"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Age-related changes are associated with mitochondrial dysfunction, which is often caused by the accumulation of mutations in mitochondrial DNA (mtDNA). One common model of aging and age-related diseases involves mice with a mutant DNA polymerase \u03b3 (PolGmut) whose proofreading function is impaired, which leads to the accumulation of mutations in mtDNA. The main limitation of such a model is that introducing a mutation into the mouse\u2019s own gene leads to the accumulation of mutations in mtDNA over several generations, making it impossible to rule out whether mtDNA mutations or compensatory effects are the cause of functional impairments such as accelerated aging. This paper describes two lines of transgenic animals with inducible expression of PolGmut. This inducible system prevents mutation accumulation in the germline, promoting stable reproduction and reproducibility of mice, increasing experimental flexibility for various studies of mitochondrial diseases. PolGmut activation at different stages of life and different tissues allows us to study the progression of pathological changes during mitochondrial aging over time and detect the onset of mutation accumulation. The simplicity, reproducibility, and temporal control of this system represent a significant methodological improvement for studying mitochondrial mutagenesis and the pathophysiology of aging. Using this model, we demonstrated that the most pronounced pathology in these animals is accelerated thymus involution and the accumulation of cytotoxic effector CD8+ T cells in the peripheral immune organs, while no significant abnormalities were observed in other organs and systems. These data probably indicate that mtDNA mutations primarily impair T-cell immune function.<\/jats:p>","DOI":"10.3390\/life15121863","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T10:50:38Z","timestamp":1764931838000},"page":"1863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ubiquitous Expression of mPolgmut Leads to the Accumulation of Cytotoxic CD8+ T Lymphocytes in Young Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4517-0042","authenticated-orcid":false,"given":"Nadezhda A.","family":"Kuznetsova","sequence":"first","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ksenia K.","family":"Kochegarova","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-3640","authenticated-orcid":false,"given":"Iuliia P.","family":"Baikova","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8170-4656","authenticated-orcid":false,"given":"Eugenii N.","family":"Korshunov","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-2102","authenticated-orcid":false,"given":"Leonid A.","family":"Ilchuk","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8834-1111","authenticated-orcid":false,"given":"Marina V.","family":"Kubekina","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2090-2488","authenticated-orcid":false,"given":"Alexandra V.","family":"Bruter","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2070-9001","authenticated-orcid":false,"given":"Yulia Yu.","family":"Silaeva","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-1216","authenticated-orcid":false,"given":"Ekaterina A.","family":"Varlamova","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology, Russian Academy of Sciences, Vavilov St., 34\/5, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ymeth.2010.05.008","article-title":"The Clinical Diagnosis of POLG Disease and Other Mitochondrial DNA Depletion Disorders","volume":"51","author":"Cohen","year":"2010","journal-title":"Methods"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41582-018-0101-0","article-title":"POLG-Related Disorders and Their Neurological Manifestations","volume":"15","author":"Rahman","year":"2019","journal-title":"Nat. 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