Veterinary Pathology最新文献

{"title":"Possible novel manifestations of papillomaviral skin disease in 4 cats, including sebaceous gland adenoma, viral plaques confined to the digits, and a viral plaque containing novel cytopathic features and felis catus type 8 DNA sequences.","authors":"John S Munday, Mirrim Kelly-Bosma, Michelle Lewis, Vicki Lim, Jesse Standage-Wardle, Micheal Hardcastle","doi":"10.1177/03009858261487716","DOIUrl":"https://doi.org/10.1177/03009858261487716","url":null,"abstract":"<p><p>Papillomaviruses (PVs) are associated with a variety of skin lesions in cats. Herein, is reported 4 cats with unusual lesions that were associated with PV infection. For each case, the lesions were examined histologically, and p16^CDKN2A protein immunolabeling was performed. Total DNA was extracted from the lesions, and both consensus and specific PCR primers were used to amplify PV DNA. In addition, <i>in situ</i> hybridization (ISH) was used to try to detect PV DNA within 2 of the lesions. Two cats had benign proliferations of sebaceous glands that contained histological changes suggestive of PV infection. Lesions from both cats were found to contain FcaPV5 DNA, although ISH was unable to localize PV DNA within either lesion. Another cat had multiple ulcerated lesions that were confined to the digits. Histology of one of these lesions was consistent with a viral plaque. The plaque contained PV-induced cell changes and FcaPV2 sequences. The fourth cat had a viral plaque that contained FcaPV8 DNA sequences. The epithelial cells within this plaque contained large spherical eosinophilic cytoplasmic bodies that have not been previously described and could therefore be unique to this FcaPV type. The findings from these 4 cats expand the range of lesions associated with FcaPVs in cats and suggest that careful evaluation of epithelial skin lesions for the possibility of an FcaPV cause is warranted. It is important to determine whether lesions are caused by PV infection due to the increased likelihood that multiple lesions will develop in affected cats.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261487716"},"PeriodicalIF":2.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169993","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":"Comparative evaluation of artificial intelligence-based and pathologist scoring of murine bile duct hyperplasia.","authors":"Ingeborg M Langohr, Dev Kumar Das, Dayananda Siddappa, Nathan Pate, Kuldeep Gautam, Sanjit Jha, Rajesh Ugalmugle, Tijo Thomas, Uttara Joshi, Srinivas Rao, Dinesh S Bangari","doi":"10.1177/03009858261485573","DOIUrl":"https://doi.org/10.1177/03009858261485573","url":null,"abstract":"<p><p>Bile duct hyperplasia in rodents, caused by chemical cytotoxicity, bile flow interference, or aging, is traditionally assessed through time-consuming microscopic examination by pathologists. We developed a deep learning-based, artificial intelligence (AI) model for quick and accurate assessment of bile duct hyperplasia in mice. The study utilized 127 hematoxylin and eosin-stained, mouse liver whole-slide images (WSIs) digitized using Aperio scanners. A segmentation algorithm with a U-Net architecture and an EfficientNet backbone was trained on 1165 areas from 35 WSIs to identify and quantify bile ducts, measure their area percentage using a supervised method, and categorize them into grades 0 to 4 using an unsupervised method. The model was validated on 24 WSIs and tested on 68 WSIs, all independently scored by 3 veterinary pathologists using consensus criteria. The segmentation model achieved Dice scores of 91.75% in training and 85.88% in validation. Testing revealed high sensitivity (95%), specificity (97%), and Dice score (95.45%), indicating robust model accuracy. Model-predicted grades showed strong correlation (<i>r</i>²_<i>s</i> = 0.86) with pathologists' consensus scores. This AI-driven approach has the potential to enhance the accuracy and efficiency of bile duct hyperplasia assessments in rodent studies, paving the way for more standardized, objective, and high-throughput histological evaluations in preclinical research.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261485573"},"PeriodicalIF":2.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170072","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":"Proliferation versus inflammation: Immunohistochemical profiling of feline chronic rhinitis and nasal lymphoma.","authors":"Sandra I C V Carvalho, Cláudia S Marques, Renata M Gaspar, Rodolfo O Leal, Rute M G Noiva","doi":"10.1177/03009858261485575","DOIUrl":"https://doi.org/10.1177/03009858261485575","url":null,"abstract":"<p><p>Lymphoma is the most common nasal cavity tumor in cats. While most recent research efforts have characterized neoplastic cell markers in feline alimentary lymphoma, only few reports are dedicated to immunohistological features of nasal lymphoid tumors beyond T- or B-cell phenotyping. In comparison, feline lymphoplasmacytic chronic rhinitis represents chronic, progressive lymphoplasmacytic inflammation, causing cyclical tissue damage and repair. Sixty-five cases of lymphoplasmacytic rhinitis and 15 cases of feline diffuse, large cell, immunoblastic nasal lymphoma were selected and submitted for immunohistochemistry to detect expression of immune markers of cell origin (CD3, CD20/PAX5, and FOXP3), proliferation (PCNA), signal transducer and activator of transcription 5 (STAT5), DNA repair (MLH1, MSH2, and MSH6), and apoptosis (BCL2). Our results indicate that neoplastic lymphocytes were predominantly CD20+/PAX5+, suggesting a B-cell phenotype. Neoplastic lymphocytes were moderately to strongly STAT5+, MLH1+, MSH6+, MSH2+, PCNA+, and FOXP3+, as well as weakly or moderately BCL2+, in most cases (n = 14/15). In both lymphoma and rhinitis cases, inflammatory lymphocytes were predominantly CD3+, while expression of DNA repair markers MLH1, MSH2, and MSH6 was occasional, varying between weak and moderate. Our results suggest that MLH1, MSH2, MSH6, PCNA, and FOXP3 show potential as diagnostic markers in differentiating lymphoma from lymphoplasmacytic rhinitis, although a diagnostic panel with MLH1, MSH6, and PCNA may suffice for diagnosing most cases where lymphoma is suspected. These findings aid in distinguishing lymphoma from inflammation and identifying potential therapeutic targets. They also suggest a regulatory B-cell phenotype in nasal lymphoma, which may aid in immune evasion.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261485575"},"PeriodicalIF":2.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171761","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":"Feline orbital mycosis: A report of 11 cases.","authors":"Milan L Piva, Erin M Scott, Jaimie L Miller, Aline Rodrigues Hoffmann, Ryan P Taylor","doi":"10.1177/03009858261485574","DOIUrl":"https://doi.org/10.1177/03009858261485574","url":null,"abstract":"<p><p>Invasive fungal infections in cats can result in sinonasal or sino-orbital disease, with brachycephalic breeds reported to be predisposed. However, a subset of cases exhibits isolated orbital signs without clinically evident sinonasal involvement, raising questions about whether the sinonasal component is genuinely absent or subclinical at the time of presentation. This retrospective study describes 11 cats with orbital mycosis lacking overt sinonasal disease, identified through the Comparative Ocular Pathology Laboratory of Wisconsin between 1998 and 2024. All 11 cats were mesocephalic breeds (10 domestic shorthair, 1 domestic longhair), with no apparent sex predilection and ages ranging from 1.5 to 17 years (median, 7 years). All cases presented with orbital disease, most commonly exposure keratitis and exophthalmos, without documented upper respiratory signs. Histologically, lesions were characterized by eosinophilic and granulomatous orbital cellulitis with central necrosis. <i>Aspergillus</i> sp. were the most common organisms identified morphologically (8/11), followed by oomycetes (2/11) and Mucorales (1/11). Panfungal polymerase chain reaction confirmed <i>Aspergillus</i> sp. in 3 cases but frequently amplified suspected contaminants. Review of published feline orbital mycosis cases revealed that mesocephalic breeds predominantly present with orbital signs, whereas brachycephalic breeds more commonly exhibit concurrent sinonasal disease. These findings suggest that orbital mycosis in mesocephalic cats may represent subclinical sinonasal infections with preferential orbital extension, potentially reflecting anatomical differences in skull conformation.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261485574"},"PeriodicalIF":2.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172338","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":"Artificial intelligence in veterinary diagnostic histopathology: Concepts, applications, and clinical implementation.","authors":"Judit M Wulcan, Jonatan Wulcan, Kevin L Jacques, Daniel G Rudmann, J Rachel Reader, Stefan M Keller","doi":"10.1177/03009858261480625","DOIUrl":"https://doi.org/10.1177/03009858261480625","url":null,"abstract":"<p><p>Artificial intelligence (AI) in human diagnostic histopathology has advanced rapidly, but clinical adoption has lagged behind research. Veterinary diagnostic pathology, being less regulated, could adopt AI faster, but the extent of its integration into diagnostic laboratories is unknown. This article combines a narrative introduction to key concepts, a scoping review of published applications, and an exploratory survey of diagnostic laboratories to provide an overview of AI in veterinary diagnostic histopathology. The narrative review highlights emerging approaches, including vision transformer-based foundation models and self-supervised learning, which may improve generalizability and reduce data requirements, although adaptation to the veterinary context remains challenging. The scoping review identified 34 studies published through a September 5, 2025, literature search, indicating steady but limited growth. Most used convolutional neural networks for relatively low-level tasks such as cell quantification, area measurement, and diagnosis. The survey had a low response rate (2 of 5 laboratories). Both respondents recognized potential benefits of AI. One laboratory had incorporated 2 AI models into routine diagnostic workflows and was evaluating additional applications, while the other had not yet implemented AI but was actively considering several models. Reported barriers included generalizability, latency, and cost. Overall, AI research in veterinary diagnostic histopathology is growing, but clinical adoption remains incompletely characterized. While less restrictive regulation may allow faster uptake than in human medicine, the lack of oversight places responsibility for validation on laboratories and pathologists. For trustworthy implementation, veterinary pathologists must understand AI fundamentals, and the field should prioritize standards for validation, transparency, and reporting.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261480625"},"PeriodicalIF":2.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138157","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":"Enhancing the translational potential of the ovine pulmonary adenocarcinoma model.","authors":"James Meehan, David Collie, Chris Cousens, Helen Brown, Ziyuan Chang, Jo Moore, Jennifer Savage, Helen Todd, Michelle L McNab, David J Griffiths, Chad E Eckert, Nicole Storer, Mark Gray","doi":"10.1177/03009858261489590","DOIUrl":"https://doi.org/10.1177/03009858261489590","url":null,"abstract":"<p><p>Ovine pulmonary adenocarcinoma (OPA) is a transmissible lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV), resulting in substantial animal welfare concerns and economic losses worldwide. We previously developed a bronchoscopic JSRV catheter instillation technique targeting the cardiac lung lobe that reliably reproduced the spectrum of OPA lesions observed in naturally occurring disease. Beyond its value for investigating JSRV pathogenesis, this experimental system provides a large animal platform for studying human lung cancer. Here, we sought to enhance its translational utility by increasing the number of virus inoculation sites and introducing a novel transbronchial intraparenchymal injection technique. Two-month-old lambs received JSRV at 4 lung sites: the left and right cardiac lobes by bronchoscopic catheter instillation and the left and right ventral diaphragmatic lobes by transbronchial intraparenchymal injection. Disease progression was monitored by monthly computed tomography, with postmortem examination and immunohistochemistry confirming OPA in 17/18 (94%) inoculated sheep. Six sheep (35%) developed advanced OPA, generating 22 gross tumors for translational studies. Bronchoscopic catheter instillation produced larger, faster-growing tumors with increased connective tissue, bronchus-associated lymphoid tissue, and intra-airway fluid, whereas intraparenchymal injection generated smaller, localized lesions. Radiomic analysis further demonstrated distinct tumor evolution between the 2 delivery methods. These findings show that both inoculation techniques are safe and effective, while also producing complementary tumor phenotypes. By increasing tumor yield per animal while generating lesions with differing growth characteristics, this refined OPA model provides a more versatile and translationally relevant platform for lung cancer research, while supporting the reduction in animal use.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261489590"},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128623","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":"Pathological significance and clinical features of myelolipomas in dogs and cats: A retrospective study of 2697 cases.","authors":"Tatiane Terumi Negrão Watanabe, Melissa M Popielarczyk, Terry G Taylor, Lavun R Franko, Alexandra K Ford, Adriana Villaseñor, Lauren W Stranahan, Emily J Brinker, Peres R Badial, Rachel L A L T Neto, Brianne Taylor, Valerie McElliott, Sunil More, Amanda L Blubaugh, Daniel R Rissi, Erin A Graham, Alexis Berrocal, Francisco R Carvallo-Chaigneau, Sai S Narayanan, Shelley J Newman, Luke Haydock, Valery Scharf, Maria Eduarda de Souza Teixeira Campos, Daniel Felipe Barrantes Murillo","doi":"10.1177/03009858261480636","DOIUrl":"10.1177/03009858261480636","url":null,"abstract":"<p><p>Myelolipomas are benign proliferations of well-differentiated adipose and hematopoietic tissue. Myelolipomas are reported to arise in the spleen, liver, and adrenal gland. Splenic myelolipomas rarely result in hemoabdomen or splenic rupture. In dogs and cats, no reports associate the formation of hematomas with splenic myelolipomas. The few published cases of myelolipoma have precluded the determination of breed and sex predisposition. A total of 2697 cases of myelolipomas were retrieved, comprising 96.3% (2596/2697) dogs and 3.7% (101/2697) cats. In dogs, splenic hematoma arising from myelolipoma was reported in 39.8% of the cases (1017/2554) and was a significant risk factor for both hemoabdomen (11.8% vs 2.0%; odds ratio [OR], 6.138; <i>P <</i> 0.001) and splenic rupture (13.9% vs 3.5%; OR, 3.898; <i>P <</i> 0.001). In cats, splenic hematoma, hemoabdomen, and splenic rupture caused by myelolipomas were infrequent, and half of the hepatic myelolipomas arose within peritoneopericardial diaphragmatic hernias (PPDH). In dogs, Labrador retrievers were the most affected breed (13.6%; 354/2596), and the mean age at the time of diagnosis was 11.4 years (range 1-18 years). The mean mass diameter was 7.4 cm (range 0.2-35 cm). The spleen (98.2%; 2550/2596) and adrenal gland (1.3%; 35/2596) were the most common locations. In cats, 53.5% (54/101) were domestic shorthairs, with a mean age of 11.1 years (range 1-18 years). The mean mass size was 2.4 cm in diameter (range 0.2-9 cm). The spleen (85.1%; 86/101) and liver (13.9%; 14/101) were the most common locations.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261480636"},"PeriodicalIF":2.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991490","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":"Disrupted development of the retina in the <i>Ccdc85c</i> knockout rat.","authors":"Shizuka Konishi, Md Mehedi Hasan, Tomoko Ogata, Miyuu Tanaka, Takeshi Izawa, Jyoji Yamate, Mitsuru Kuwamura","doi":"10.1177/03009858261477041","DOIUrl":"https://doi.org/10.1177/03009858261477041","url":null,"abstract":"<p><p>The <i>coiled-coil domain-containing 85c</i> (<i>Ccdc85c</i>) knockout (KO) rat generated by genome editing exhibits hydrocephalus and subcortical heterotopia. In this study, we aimed to further investigate the function of CCDC85C protein in the development of the retina. Expression of CCDC85C, acetylated tubulin, ciliary rootlet coiled-coil protein (CROCC), zonula occludens-1 (ZO-1), glutamine synthetase, and PAX6 were examined immunohistochemically in wild-type F344 rats at embryonic day (ED) 19 and at postnatal days (PNDs) 0, 4, 6, 13, and 20. Immunoelectron microscopy was performed for CCDC85C in the normal rat retina. Retinal lesions in <i>Ccdc85c</i> KO rats were examined using fundus photography, optical coherence tomography (OCT), and histology. In the normal rat retina, CCDC85C was co-localized with ZO-1 in the outer limiting membrane and persistently expressed after ED19. Ultrastructurally, CCDC85C was located between the outer nuclear layer and the inner segments, and showed the same location as the tight junction. In <i>Ccdc85c</i> KO rats, multifocal retinal dysplasia; disarrangement of the inner and outer segments, cilia, and rootlets; and impaired development of Müller cells were observed. In OCT images, <i>Ccdc85c</i> KO rats showed parallel hyperintense striations in the inner nuclear layer, and low reflectivity of the outer limiting membrane and layer of rods and cones. These results suggest that CCDC85C protein is located in the tight junction complex and is involved in retinal layer formation. The <i>Ccdc85c</i> KO rat model provides a novel tool to study retinal development as well as genetic hydrocephalus.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261477041"},"PeriodicalIF":2.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892061","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":"Quantitative analysis of artificial intelligence-based detection of subregions from murine ear skin sections with application to quantifying drug-induced epidermal hyperplasia.","authors":"Brewster Curry, Nicolle Bejarano Villalba, Sarah R Vargas, Katherine Hammerman, Yutian Zhan, Susan Fish, Martin Hegen, Charles Halsey, Sripad Ram","doi":"10.1177/03009858261480627","DOIUrl":"https://doi.org/10.1177/03009858261480627","url":null,"abstract":"<p><p>The advent of artificial intelligence (AI) technologies is creating a paradigm shift in drug discovery and development. Veterinary pathology is an area that can significantly benefit from AI tools. The availability of AI algorithms in commercial software packages such as HALO and Visiopharm has generated interest in automating pathologists' workflows for the detection and quantification of histology endpoints from whole-slide images. As each software package provides a distinct set of AI models, the relative performance and equivalency of these models for lesion detection and quantification are poorly understood. Here, we present a systematic comparison of the performance of AI algorithms developed in HALO and Visiopharm. Specifically, we trained AI algorithms in HALO and Visiopharm by using the same ground truth training data to detect different subregions and quantify their areas from hematoxylin and eosin (HE)-stained images of murine skin sections. We also calculate the performance metrics (precision, recall, <i>F</i>1 score) for each algorithm using the same test dataset. Our analysis shows that both HALO and Visiopharm algorithms have comparable performance and are resilient to training data size and changes in the color profile of the HE images. As an application, we compared the results of the AI algorithms against pathologists' scores to quantify epidermal hyperplasia. Our analysis shows that the quantitative data from AI algorithms are consistent with pathologists' scores. These results provide a quantitative characterization of commercially available AI models in HALO and Visiopharm and offer practical guidelines for designing and validating AI algorithms using these software packages.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858261480627"},"PeriodicalIF":2.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888172","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 the progressive neuroaxonal dystrophy and subsequent gait abnormalities in the <i>Hspa8</i>^<i>V95E</i> knock-in rats.","authors":"Takahiro Sekiguchi, Miyuu Tanaka, Ryoko Fujikawa, Takashi Kuramoto, Takeshi Izawa, Mitsuru Kuwamura","doi":"10.1177/03009858261428505","DOIUrl":"10.1177/03009858261428505","url":null,"abstract":"<p><p>Neuroaxonal dystrophy is a group of genetic neurodegenerative diseases that are histopathologically characterized by swollen axons (spheroids). We previously established a novel rat model of neuroaxonal dystrophy harboring a V95E missense mutation in the <i>heat shock protein family A (HSP70) member 8</i> (<i>Hspa8</i>) gene that originally emerged by ENU-induced random mutagenesis. <i>Hspa8</i>^<i>V95E</i> mutant rats show marked spheroid formation in the central nervous system and develop progressive hind limb ataxia. However, the detailed pathology of <i>Hspa8</i>^<i>V95E</i> mutant rats remains to be elucidated. In the current study, we examined the characteristics of gait abnormalities and the detailed distribution of spheroids in the central nervous system of <i>Hspa8</i>^<i>V95E</i> knock-in (KI) rats. Using footprint tests, we demonstrated the increased ratio of step width to step length (outward step) of the hind limbs in <i>Hspa8</i>^<i>V95E</i> KI rats from 3 weeks of age. In <i>Hspa8</i>^<i>V95E</i> KI rats aged 15 weeks, spheroids were predominantly distributed in the proprioceptive sensory pathway from the lower body, including the gracile fasciculus and the nucleus. The number of spheroids increased with age and was accompanied by glial reactions in the dorsal funiculus. Moreover, we observed the accumulation of kinesin light chain 1; kinesin heavy chain isoforms 5A, -5B, and -5C; and microtubule-associated protein light chain 3 B in the spheroids and degenerated axons of <i>Hspa8</i>^<i>V95E</i> KI rats at 13 weeks of age. Collectively, our data suggest the involvement of impaired axonal transport and autophagy in spheroid formation in <i>Hspa8</i>^<i>V95E</i> mutant rats.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"927-937"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435958","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}