Female Hsd:Athymic nude-Foxn1nu sentinel mice spontaneously develop a life-limiting protein-losing nephropathy. We aimed to characterize this disease and identify risk factors. Affected mice presented with anasarca and pale tan, irregularly pitted kidneys. Histologically, glomeruli were distorted by eosinophilic, hyaline, mesangial deposits. Additional non-specific glomerular changes included synechiae, periglomerular fibrosis, and capillary thrombosis. Ectatic tubules with attenuated epithelium and tubular casts and interstitial inflammation were also present. Mesangial deposits were Congo red (CR)-negative, periodic acid-Schiff-positive, and pale blue to pink using Masson's trichrome stain. The glomerular basement membrane was mildly irregular using Jones' methenamine silver stain. The mesangial deposits were immunoglobulin G (IgG)- and immunoglobulin A (IgA)-immunonegative and immunoglobulin m (IgM)-immunopositive. Ultrastructurally, subendothelial electron-dense deposits were composed of straight and curved linear, 30 to 170 nm diameter tubular, and 9 to 16 nm diameter fibrillary profiles. Together, these findings were consistent with hyaline glomerulopathy due to IgM deposition. Prevalence of the disease over 6 years was 0.6% (75/13 042 homozygous sentinel mice). Vivarium biosecurity level, infectious disease screening results, and comorbidities were evaluated in 75 female, 6-month-old, homozygous nude sentinel mice with hyaline glomerulopathy and 75 without. Neither biosecurity level nor pathogen diversity was risk factors. However, sentinel mice with auto-inflammatory conditions, such as proliferative typhlocolitis (P = .005) and dermatitis (P = .03), and with lymphoid neoplasia (lymphoma; P = .0007) had a lower risk of developing hyaline glomerulopathy. Our results support the diagnosis of hyaline glomerulopathy in young adult, female, nude sentinel mice and help recognize this spontaneous condition in a canonical immunodeficient research model.

The SDRG rat, characterized by a Sprague-Dawley (SD) genetic background with deletion of Rag1 and Il2rg genes, has deficiencies in B, T, and natural killer (NK) cells, making it a valuable model for preclinical applications such as tissue transplantation/humanization and assessment of advanced therapeutic products. Limited data exists on spontaneous background findings in this strain, particularly in aging animals. To address this gap, this study investigated clinical and anatomical pathology findings in 83 SDRG rats (40 males and 43 females), aged 10 to 26 weeks. Analyses included hematology, clinical chemistry, bone marrow smears, blood immunophenotyping, necropsy, and histology. Hematology revealed severely reduced lymphocyte counts, with a mild age-related increase in counts. Compared with SD rats, both sexes of SDRG rats had higher neutrophil, monocyte, and eosinophil counts; increased urea and cholesterol; lower albumin and total protein; and higher age-related glutamate dehydrogenase concentrations. Males had longer prothrombin times, while females showed sporadic age-related increases in alanine aminotransferase, aspartate aminotransferase, and triglycerides. Blood immunophenotyping confirmed the absence of circulating B and T lymphocytes and NK cells, alongside increased monocytes. Salient microscopic findings included lymphoid organ hypoplasia and inflammation in kidneys and lungs, with urinary bacterial infections, contributing to a single mortality. Age-related changes included progressive cardiomyopathy, early chronic progressive nephropathy, and early reproductive senescence in females. These findings underscore the SDRG strain's potential as a model for preclinical evaluations of cell-based products and provide an initial reference into background features of this immunodeficient model that might help interpretations of experimental results.

Ulcerative dermatitis is common in captive cephalopods and often results from trauma to their delicate epidermis with subsequent infection by opportunistic pathogens. We report 3 cases of fatal ulcerative dermatitis caused by a rare pathogen in a cohort of captive, adult, north Pacific big eye octopuses (Octopus californicus). Abundant, 5 to 8 µm diameter, roughly spherical organisms, often located in pairs or clusters, were infiltrating the ulcers in all 3 cases. Ultrastructurally, the organisms possessed multilamellated to scaley cell walls and were surrounded by empty, irregularly ovoid, 1 μm diameter, membrane-bound structures consistent with an ectoplasmic net. These features are consistent with thraustochytrid, a marine saprophyte. Previous reports of pathogenic thraustochytrid infections in cephalopods are rare, suggesting this is an uncommon albeit serious infection in captive cephalopod populations.

Seven cutaneous mast cell tumors were identified in 6 geriatric California sea lions (Zalophus californianus). All tumors were within the dermis and grossly appeared as single, or in one case two, less than 1-cm-diameter, well-circumscribed, raised nodules. The majority (6/7) of the neoplasms occurred near mucocutaneous junctions (eyelid, lip, or anus). The mast cell tumors were composed of round cells arranged in sheets with poorly granulated cytoplasm or an absence of cytoplasmic granules in routine hematoxylin and eosin-stained sections. Cytology (n = 1) showed adequate staining of mast cell granules with Diff-Quik and Wright-Giemsa stains. Immunohistochemistry for cKIT revealed cytoplasmic to membranous immunoreactivity in all tumors. Giemsa staining for metachromatic granules was inconsistent. No local recurrence or metastasis has been observed in the 5 living individuals with follow-up periods ranging from 6 to 42 months. Given these findings, similar poorly granulated mast cell tumors in geriatric California sea lions are suspected to have biologically benign behavior.

Mycobacteria (Mycobacteriaceae family) comprise five genera (Mycobacterium, Mycolicibacterium, Mycolicibacter, Mycolicibacillus, and Mycobacteroides), which include relevant animal and human pathogens. Histology is a rapid method for preemptively diagnosing mycobacteriosis, contributing to surveillance, control, and eradication. A constraint on histology is the limited sensitivity and specificity of acid-fast stains, as the number of detectable bacilli in formalin-fixed paraffin-embedded (FFPE) tissue varies and other microorganisms are acid-fast positive. Immunohistochemistry has low specificity and is cross-reactive with other bacteria. We developed an RNAscope probe-based in situ hybridization (ISH) assay, targeting a conserved sequence of 16S rRNA gene of Mycobacteriaceae, and tested it on archived FFPE tissues from 22 mammals, birds, amphibians, and fish, collected between 1999 and 2024, infected with 23 species of mycobacteria of veterinary importance, and tissue from 7 animals infected with other bacteria. Mycobacterium spp. (n = 17), Mycobacteroides spp. (n = 2), Mycolicibacter spp. (n = 1), and Mycolicibacterium spp. (n = 3) confirmed infected tissues were tested, and results were compared with 2 acid-fast stains, Ziehl-Neelsen and Fite-Faraco, and Mycobacterium spp. PCR from FFPE tissues. Hybridization signals were detected in all FFPE tissues, archived for up to 25 years, with confirmed Mycobacterium spp. (17/17; 100%), Mycobacteroides spp. (2/2), Mycolicibacter spp. (1/1), and Mycolicibacterium spp. (3/3), including cases with few or no acid-fast bacilli. Available FFPE tissues were positive by PCR (15/15, 100%). Hybridization signal was not identified in other bacterial infections. This ISH assay is a rapid screening and specific diagnostic tool for mycobacteria in FFPE tissues.

The vacuole formation (VF) rat is an autosomal recessive myelin mutant characterized by generalized tremor, hypomyelination, and periaxonal VF of the central nervous system. We previously identified a nonsense mutation in the DOP1 leucine zipper-like protein A (Dop1a, also known as Dopey1) gene located on rat chromosome 8. In this study, we investigated the kinetics of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes by assessing the expression patterns of transcription factors that are involved in oligodendrocyte development. The number of small, round oligodendrocytes lacking distinct cellular processes, immunolabeled with anti-adenomatous polyposis coli (APC, clone CC1) antibody, was increased in the spinal cords of the VF rats, suggesting a disrupted maturation of oligodendrocytes. In addition, the terminal differentiation and maturation of OPCs into myelinating mature oligodendrocytes may be impaired and compensatory myelination largely could fail in the VF rat. Our findings also demonstrated that the DOP1A protein is expressed in OPCs as well as mature oligodendrocytes. Finally, the intracellular trafficking of myelin basic protein (Mbp) mRNAs may be disrupted in oligodendrocytes of the VF rats. Our data suggested that DOP1A dysfunction causes impaired differentiation and maturation of oligodendrocyte-lineage cells, resulting in hypomyelination and an impaired compensatory myelination.

Aliarcobacter butzleri is a Campylobacter-like bacteria associated with watery diarrhea in humans and is infrequently reported in nonhuman primate (NHP) populations. While clinical and microscopic features in humans are indistinguishable from Campylobacter spp. infection, descriptions of A. butzleri-associated colitis in NHP are lacking. Here, we describe the clinical and pathological features of diarrhea and colitis associated with A. butzleri in rhesus macaques using a retrospective approach. Over a 3-year period, A. butzleri was isolated from 10 macaques with diarrhea. Five of the 10 were submitted for necropsy and had features of chronic enterocolitis, consistent with existing literature. However, 40% (2/5) of the cases were characterized by ulcerative colitis, which has not previously been described as a feature of A. butzleri colitis. A. butzleri should be considered a differential diagnosis in cases of diarrhea and enterocolitis in captive rhesus macaques.