{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:33:14Z","timestamp":1777919594082,"version":"3.51.4"},"reference-count":53,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2017 Prot. 20175XHBPN"],"award-info":[{"award-number":["PRIN 2017 Prot. 20175XHBPN"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Immunodeficient mouse strains are widely used in several fields of biomedical research. Despite that, no standardized system for evaluating immunodeficiency in mice currently exists, and an unbiased comparison of various immunodeficient mouse strains is difficult. The aim of our study was to develop a standardized multi-disciplinary protocol for the morpho-phenotypical assessment of immunodeficient mouse models. We selected 4 immunodeficient strains of mice (\n                    <jats:italic toggle=\"yes\">Cd40l<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    ,\n                    <jats:italic toggle=\"yes\">Was<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    ,\n                    <jats:italic toggle=\"yes\">Rag1<\/jats:italic>\n                    <jats:italic toggle=\"yes\">\n                      <jats:sup>R972Q\/R972Q<\/jats:sup>\n                    <\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Rag1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    ) on a C57BL\/6J genetic background and a group of control C57BL\/6J wild-type mice. The lymphoid organs were harvested, weighed, and analyzed by histology, immunohistochemistry, and flow cytometry. Hematology and bone marrow cytology were also performed. The main immune cell populations were investigated, including lymphocytes, monocytes\/macrophages, neutrophils, and natural killer cells. Relative organ weights were lower in the strains with the highest level of immunodeficiency (\n                    <jats:italic toggle=\"yes\">Rag1<\/jats:italic>\n                    <jats:italic toggle=\"yes\">\n                      <jats:sup>R972Q\/R972Q<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Rag1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    ). Histology revealed overall lower cellularity in the same strains, particularly in\n                    <jats:italic toggle=\"yes\">Rag1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. Tissue spatial distributions of the immune cell populations were confirmed by immunohistochemistry, while flow cytometry allowed for their relative quantification. Likewise, hematology detected moderate lymphopenia in the\n                    <jats:italic toggle=\"yes\">Rag1<\/jats:italic>\n                    <jats:italic toggle=\"yes\">\n                      <jats:sup>R972Q\/R972Q<\/jats:sup>\n                    <\/jats:italic>\n                    mice and more severe lymphopenia in\n                    <jats:italic toggle=\"yes\">Rag1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. Our protocol has proven itself effective for the morpho-phenotypical assessment of the immunodeficient mouse models under investigation and was useful in characterizing the type and severity of the defects. The different laboratory techniques were consistent in the characterization and confirmation of immunodeficiency in the different strains, providing different complementary insights.\n                  <\/jats:p>","DOI":"10.1177\/03009858251361517","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:40:15Z","timestamp":1756384815000},"page":"149-163","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A standardized protocol for assessing immunodeficiency in mouse models"],"prefix":"10.1177","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-528X","authenticated-orcid":false,"given":"Andrea","family":"Cappelleri","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Animal Sciences, University of Milan, Lodi, Italy"},{"name":"Mouse and Animal Pathology Laboratory (MAPLab), UniMi Foundation, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9561-5248","authenticated-orcid":false,"given":"Simone","family":"Canesi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Sciences, University of Milan, Lodi, Italy"},{"name":"Mouse and Animal Pathology Laboratory (MAPLab), UniMi Foundation, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1851-1429","authenticated-orcid":false,"given":"Valentina","family":"Capo","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy"},{"name":"National Research Council, Institute of Genetic and Biomedical Research, Milan Unit, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Zecchillo","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy"},{"name":"Translational and Molecular Medicine (DIMET), University of Milano Bicocca, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi D.","family":"Notarangelo","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Draghici","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Bettoni","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Sciences, University of Milan, Lodi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Sciences, University of Milan, Lodi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierangelo","family":"Moretti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Turin, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Villa","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy"},{"name":"National Research Council, Institute of Genetic and Biomedical Research, Milan Unit, 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