Veterinary Pathology最新文献

{"title":"Histological and ultrastructural analysis of regional variations in Negri bodies with inner bodies in naturally infected rabid dogs.","authors":"Boonkanit Markbordee, Alpha Grace B Cabic, Nuttipa Iamohbhars, Nozomi Shiwa-Sudo, Kazunori Kimitsuki, Mark Joseph M Espino, Leilanie B Nacion, Daria L Manalo, Satoshi Inoue, Chun-Ho Park","doi":"10.1177/03009858261441529","DOIUrl":"https://doi.org/10.1177/03009858261441529","url":null,"abstract":"<p><p>Negri bodies (NBs) are cytoplasmic inclusions associated with rabies virus infection and are a characteristic histopathologic feature of rabies. Although their morphology has been described in humans and experimental animal models, detailed characterization in naturally infected dogs remains limited. The objective of this study was to characterize the histopathologic, immunophenotypic, and ultrastructural features of NBs in naturally infected dogs from the Philippines. Brain tissues from 24 dogs were examined by routine histology, special stains, immunohistochemistry, and indirect immunofluorescence. Transmission electron microscopy was performed in 6 selected cases. In the cerebrum, hippocampus, and cerebellum, NBs were predominantly composed of abundant matrix material and occasionally contained inner bodies (classic NBs), with variable association with bullet-shaped virions and ribosomes. These inclusions were immunoreactive for rabies virus nucleoprotein and phosphoprotein and stained positively with luxol fast blue. Inner bodies were immunoreactive for glycoprotein and matrix protein and were positive with silver impregnation, Nissl, and Bodian stains. In contrast, small inclusions (lyssa bodies) identified in the thalamus and brainstem consisted mainly of immature viral particles with minimal matrix material. Collectively, these findings indicate region-dependent ultrastructural variation in rabies virus-associated inclusions in naturally infected dogs, while supporting a shared viral origin among the different morphologic forms. This characterization further supports the diagnostic value of these inclusions in veterinary neuropathology.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261441529"},"PeriodicalIF":1.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural pathology and temporal patterns of viral replication and lesion development following mouse kidney parvovirus infection in B6, CD1, and NSG mice.","authors":"Ileana C Miranda, Mandy L Kain, Amanda C Ritter, Rodolfo J R Arbona, Anibal G Armien, Neil S Lipman, Sébastien Monette","doi":"10.1177/03009858261420394","DOIUrl":"10.1177/03009858261420394","url":null,"abstract":"<p><p>Mouse kidney parvovirus (MKPV) causes inclusion body nephropathy, resulting in clinical signs and mortality in immunodeficient mice and subclinical infection in immunocompetent mice. While late-stage renal lesions and viral replication have been characterized, a comprehensive multisystemic investigation of MKPV infection from the initial to the late stages of infection has not been conducted. Our goal was to investigate lesions and viral replication in all major organs at multiple stages of MKPV infection in immunocompetent C57BL/6NCrl (B6) and Crl: CD1(ICR) (CD1) mice and immunodeficient NOD. Cg-<i>Prkdc</i>^<i>scid</i><i>Il2rg</i>^{<i>tm1Wjl</i>}/SzJ (NSG) mice. Following experimental oronasal inoculation with MKPV, mice were evaluated at 15 time points from 1.5 to 112 days post-inoculation (DPI) by histology and <i>in situ</i> hybridization for MKPV RNA on all major organs, as well as immunohistochemistry for markers of immune cells and renal tubular injury. In all strains, the gastrointestinal mucosa was the initial site of viral replication beginning at 3 DPI and persisting through the study without associated lesions. In B6 and CD1 mice, viral replication was first detected in renal tubules on 28 and 14 DPI, respectively, and lymphoplasmacytic tubulointerstitial nephritis was first evident on 63 and 49 DPI, respectively. B6 mice displayed the lowest levels of renal viral replication and lesion severity. In contrast, renal viral replication was highest in NSG mice; the virus was first detected on 42 DPI and in association with tubular degeneration from 63 DPI. Electron microscopy on kidney tissues of infected mice revealed parvoviral virions, nuclear replication, and assembly compartments for the first time.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"542-560"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Image Challenge in <i>Veterinary Pathology</i>.","authors":"","doi":"10.1177/03009858251395280","DOIUrl":"https://doi.org/10.1177/03009858251395280","url":null,"abstract":"","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":"63 3","pages":"391-392"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Image challenge in <i>Veterinary Pathology</i>, answers: Diseases in humanized mice.","authors":"","doi":"10.1177/03009858251395282","DOIUrl":"https://doi.org/10.1177/03009858251395282","url":null,"abstract":"","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":"63 3","pages":"562-563"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Clostridium cuniculi</i> is associated with chronic high-morbidity low-mortality diarrhea in NSG and NSG-related mouse strains.","authors":"Kerriann M Casey, Rina Barouch-Bentov, Wencke Reineking, Flavio H Alonso, Roberta Moorhead, Minoo Fazel, Anibal G Armien, Francisco A Uzal, Rachael B Chanin, Ami S Bhatt, Sherril L Green, Stephen A Felt, Claude M Nagamine","doi":"10.1177/03009858251372565","DOIUrl":"10.1177/03009858251372565","url":null,"abstract":"<p><p>In October 2020, adult male and female NSG (NOD. Cg-<i>Prkdc</i>^<i>scid</i> <i>Il2rg</i>^{<i>tm1Wjl</i>}/Sz) mice were reported for diarrhea within a mouse barrier facility. Other immunodeficient strains harboring the SCID (<i>Prkdc</i>^<i>scid</i>) or <i>Rag</i> (<i>Rag</i>^<i>null</i>) mutations together with the <i>IL2rg</i> (<i>Il2rg</i>^<i>null</i>) mutation were affected. At its peak, over 20 laboratories in 10/16 (62.5%) barrier rooms were affected. Mortality was rare except in lactating females (≥ P11). Grossly, nonlactating adult female and male mice (n = 16) had mild to moderate, small and large intestinal distension with corresponding individual cell death and sloughing of superficial enterocytes in the cecocolonic mucosa. Lactating NSG dams (n=6) had moderate to severe gastrointestinal distension and/or segmental, dark red to gray, small intestinal discoloration. In addition to the same histologic lesions seen in nonlactating female NSG mice, lactating NSG dams often had severe ulcerative inflammation affecting the jejunum, ileum, cecum, and colon. Traditional ancillary diagnostic tests including aerobic and anaerobic cultures (blood, liver, spleen, and intestines), fecal PCR, and fecal floatation failed to yield a causative organism. Further cohousing and oral gavage studies determined neither immunocompetent CD1 (Crl:CD1 [ICR]) mice nor immunodeficient NOD scid (NOD.Cg-<i>Prkdc</i>^<i>scid</i>/J) and <i>Rag2</i> KO (C57BL/6. Cg-<i>Rag2</i>^{<i>tm1.1Cgn</i>}/J) mice were susceptible to clinical disease. Extensive control barriers were implemented including a veterinary-managed NSG breeding barrier, alterations in husbandry practices, and strategic environmental disinfection, allowing for continuity of experimental studies while avoiding widespread depopulation of the barrier. Subsequent strain-resolved metagenomics and qPCR assay development identified <i>Clostridium cuniculi</i> and its enterotoxin exclusively within diarrheic mice.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"528-541"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathology associated with human CAR T cell administration in NOD.Cg-<i>Prkdc</i>^<i>scid</i><i>Il2rg</i>^{<i>tm1Wjl</i>}/SzJ (NSG) mice: A retrospective analysis.","authors":"Renata M Mammone, Elinor Willis, Pedro Ruivo, Giovanni E Finesso, Arin Cox, Charles-Antoine Assenmacher, Enrico Radaelli, Alessandra Piersigilli, Ileana C Miranda","doi":"10.1177/03009858251409216","DOIUrl":"10.1177/03009858251409216","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for neoplasia and autoimmune diseases. Immunocompromised mice are a common model to test the efficacy and safety of CAR T cells of human origin. Preclinical toxicity associated with human CAR T-cell products encompasses a spectrum of morphologic changes, with currently limited documentation in the scientific literature. The purpose of this retrospective study was to characterize the histopathologic features associated with human CAR T-cell administration in immunodeficient NOD.Cg-<i>Prkdc</i>^<i>scid</i> <i>Il2rg</i>^{<i>tm1Wjl</i>}/SzJ (NSG) mice (<i>n</i> = 392) submitted to 3 different academic institutions in the United States between 2017 and 2024. Lesions were categorized into xenogeneic graft-versus-host disease (xGvHD) (<i>n</i> = 287), aberrant proliferation of human T cells (<i>n</i> = 188), vascular pathologies (<i>n</i> = 66), on-target/off-tumor (OTOT) toxicity (<i>n</i> = 44), immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) in mice previously humanized with human CD34+ hematopoietic stem cells (HSCs) (<i>n</i> = 21), and acute lysis syndrome (ALS) (<i>n</i> = 5). This study provides veterinary pathologists with descriptive guidance on the pathology associated with human CAR T-cell therapy in immunodeficient mice. Additional molecular data and detailed information related to each construct are necessary to further investigate the translatability of such liabilities to the clinical setting.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"462-477"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: A preamble to the pathology of humanized mouse models.","authors":"Enrico Radaelli, Pedro Ruivo, Charles-Antoine Assenmacher","doi":"10.1177/03009858261430733","DOIUrl":"https://doi.org/10.1177/03009858261430733","url":null,"abstract":"","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":"63 3","pages":"393-396"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of host immune cell infiltrate in human CAR T cell-mediated xenogeneic graft versus host disease in NSG mice.","authors":"Elinor Willis, Esha Banerjee, Jillian Verrelle, Arin Cox, Charles-Antoine Assenmacher, Enrico Radaelli","doi":"10.1177/03009858251391388","DOIUrl":"10.1177/03009858251391388","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cells are revolutionary cancer therapies that are Food and Drug Administration-approved for hematologic malignancies and under investigation for solid tumors. The use of allogeneic over autologous CAR T cells offers advantages, including broader availability and reduced costs. However, allogeneic CAR T cells frequently trigger graft versus host disease (GvHD), a complication observed in patients and experimental models where human CAR T cells are delivered into immunocompromised mice. To understand the contribution of the mouse immune response to human CAR T cell-mediated xenogeneic GvHD, we analyzed GvHD lesions in a human xenograft tumor model in NOD.Cg-<i>Prkdc</i>^scid <i>Il2rg</i>^tm1Wjl/SzJ (NSG) mice. The animals were treated with second-generation CAR T cells targeting a human tumor-specific antigen without a murine homolog. Mice treated with CAR T cells had more severe GvHD lesions than control mice receiving nontransduced (NT) T cells. Also, tumor burden was negatively correlated with GvHD lesion severity. Immunohistochemical characterization of the GvHD lesions showed that approximately 45% of the immune cell infiltrate consisted of murine cells, most of which were IBA1+ histiocytes, with a small population of CD11c+ dendritic cells. The murine histiocytes expressed activation/antigen presentation markers, including high levels of the costimulatory molecule CD86. Analysis of macrophage polarization indicated an M2-like phenotype. These findings demonstrate a significant contribution of the mouse histiocytic compartment to lesions of human CAR T cell-mediated xenogeneic GvHD. Our results suggest that CD86+ murine antigen-presenting cells help trigger and sustain the xenoreactive CAR T cell response. Furthermore, xenogeneic GvHD exhibits a shift toward M2 polarization in murine macrophages.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"490-499"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous and experimentally induced lesions in NOD-scid gamma and other NOD-derived mouse strains.","authors":"Pedro Ruivo, Renata Mammone, Ileana C Miranda, Sebastian E Carrasco, Sebastien Monette, Laura Janke, Heather Sheppard, Charles-Antoine Assenmacher, Denise M Imai, Alessandra Piersigilli, Sara F Santagostino, Enrico Radaelli","doi":"10.1177/03009858251403172","DOIUrl":"10.1177/03009858251403172","url":null,"abstract":"<p><p>Immunodeficient mice, particularly the NOD.Cg-<i>Prkdc</i>^<i>scid</i><i>Il2rg</i>^{<i>tm1Wjl</i>}/SzJ (NSG) strain and other non-obese diabetic (NOD)-derived lines are widely used in biomedical research due to their profound immunosuppression, which enables stable engraftment of human cells and tissues with minimal rejection. Despite their broad utility, these models exhibit unique immunologic and anatomic features and are predisposed to infectious and noninfectious diseases that may confound experimental outcomes and limit translational relevance. This review summarizes current knowledge on spontaneous, infectious, and experimentally induced lesions in NSG and related strains. These mice characteristically display hypoplastic lymphoid organs, including the spleen, thymus, and lymph nodes, due to a near-complete absence of lymphocytes. Spontaneous background lesions include splenic osseous metaplasia, neurodegeneration, pancreatic mastocytosis, cochlear degeneration, intervertebral disk disease, skull hyperostosis, and pancreatic duct cysts, among others. Common spontaneous neoplasms include lymphomas, osteosarcomas, and mammary gland tumors. Due to their immunodeficient status, NSG and NOD-derived mice are also highly susceptible to opportunistic infections, such as <i>Corynebacterium bovis</i>, <i>Chlamydia muridarum</i>, <i>Clostridioides difficile</i>, and mouse kidney parvovirus. In humanized models, engraftment of human immune cells can result in distinctive syndromes, including xenogeneic graft-versus-host disease, post-transplant lymphoproliferative disorders, and chimeric myeloid cell hyperactivation syndrome, which can impact study outcomes and lead to mortality and morbidity. This review is intended as a resource for comparative pathologists to become familiar with these widely used immunodeficient mice, so they can interpret strain-specific lesions and recognize experimental confounders in these mouse models.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"397-422"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of humanized mice applications in regulatory submissions for cell and gene therapy products.","authors":"Giovanni Pellegrini, Lucia Minoli, Sara Degl'Innocenti, Michela Gabaldo, Valeria Bertani, Alessandra Piersigilli, Francesca Sanvito, Patrizia Cristofori","doi":"10.1177/03009858251411297","DOIUrl":"10.1177/03009858251411297","url":null,"abstract":"<p><p>The emergence of cell and gene therapies has transformed the therapeutic landscape, offering curative potential for a range of previously intractable diseases. However, their biological complexity and patient-specific mechanisms of action present significant challenges for preclinical evaluation, particularly in modeling human responses and predicting safety outcomes. Traditional animal models often lack translational fidelity, prompting the adoption of humanized immunodeficient mice, including those engrafted with human immune cells, as more predictive in vivo platforms. These models enable the assessment of pharmacodynamics, biodistribution, and immunotoxicity in a human-relevant context. This review critically explores the integration of humanized mice into regulatory submissions for cell and gene therapy products, highlighting their utility across proof-of-concept, pharmacokinetic, toxicology, and tumorigenicity studies. We also address key limitations of the different models, including variability in engraftment efficiency, immune reconstitution, and lifespan, as well as challenges in standardization and regulatory acceptance. Future directions include refining humanized mouse models to better mimic human physiology, incorporating pathological endpoints, and aligning with 3R principles and new methodological approaches. By enhancing the translational relevance of nonclinical data, humanized mice are poised to play an increasingly strategic role in early safety assessment and successful development of advanced therapies.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"423-444"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}