Experimental mouse models are central to basic biomedical research; however, variability exists across genetically identical mice and mouse facilities making comparisons difficult. Whether specific indigenous gut bacteria drive immunophenotypic variability in mouse models of human disease remains poorly understood. We performed a large-scale experiment using 579 genetically identical laboratory mice from a single animal facility, designed to identify the causes of disease variability in the widely used dextran sulphate sodium mouse model of inflammatory bowel disease. Commonly used treatment endpoint measures—weight loss and intestinal pathology—showed limited correlation and varied across mouse lineages. Analysis of the gut microbiome, coupled with machine learning and targeted anaerobic culturing, identified and isolated two previously undescribed species, Duncaniella muricolitica and Alistipes okayasuensis, and demonstrated that they exert dominant effects in the dextran sulphate sodium model leading to variable treatment endpoint measures. We show that the identified gut microbial species are common, but not ubiquitous, in mouse facilities around the world, and suggest that researchers monitor for these species to provide experimental design opportunities for improved mouse models of human intestinal diseases.

Regulatory T cells (T _regs ) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident T _regs and group 2 innate lymphoid cells (ILC2s); however, how T _regs locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of T _reg function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and T _regs engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3 ^high T _regs , which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-T _reg communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3 ^high T _regs can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-T _reg interactions represent a critical feedback mechanism to control adaptive type 2 immunity.

Canine apocrine gland anal sac adenocarcinoma (AGASAC) is a malignant tumour with variable clinical progression. The objective of this study was to use robust multivariate models, based on models employed in human medical oncology, to establish clinical and histopathological risk factors of poor survival. Clinical data and imaging of 81 cases with AGASAC were reviewed. Tissue was available for histological review and immunohistochemistry in 49 cases. Tumour and lymph node size were determined using the response evaluation criteria in the solid tumours system (RECIST). Modelling revealed tumour size over 2 cm, lymph node size grouped in three tiers by the two thresholds 1.6 cm and 5 cm, surgical management, and radiotherapy were independent clinical variables associated with survival, irrespective of tumour stage. Tumour size over 1.3 cm and presence of distant metastasis were independent clinical variables associated with the first progression-free interval. The presence of the histopathological variables of tumour necrosis, a solid histological pattern, and vascular invasion in the primary tumour were independent risk factors of poor survival. Based upon these independent risk factors, scoring algorithms to predict survival in AGASAC patients are presented.

Cancer is a common cause of morbidity and mortality in domestic cats. Because the mutational landscape of domestic cat tumors remains uncharacterized, we performed targeted sequencing of 493 feline tumor–normal tissue pairs from 13 tumor types, focusing on the feline orthologs of ~1000 human cancer genes. TP53 was the most frequently mutated gene, and the most recurrent copy number alterations were loss of PTEN or FAS or gain of MYC . By identifying 31 driver genes, mutational signatures, viral sequences, and tumor-predisposing germline variants, our study provides insight into the domestic cat oncogenome. We demonstrate key similarities with the human oncogenome, confirming the cat as a valuable model for comparative studies, and identify potentially actionable mutations, aligning with a “One Medicine” approach.

Case summary: Feline sino-nasal aspergillosis is a rare condition with only sparse heterogeneous reports in the literature regarding its treatment. This report describes the presentation, treatment and outcome of a cat with sino-nasal aspergillosis treated by meticulous debridement in combination with topical and systemic azole therapy. Diagnosis was based on MRI, in combination with rhinoscopic assessment and visualisation of fungal plaques, followed by histopathology, fungal culture and panfungal PCR. The cat was treated by debridement of fungal plaques via anterior rhinoscopy and frontal sinusotomy and local instillation of 1% clotrimazole solution, followed by a 4-week course of oral itraconazole. Histopathology confirmed fungal rhinitis and culture identified Aspergillus fumigatus and Aspergillus versicolor. Clinical remission was achieved after treatment; however, evidence of persistent infection was confirmed in the post-mortem examination 8 months after the cat was euthanased for unrelated reasons. Relevance and novel information: Despite clinical remission, the persistence of fungal infection post mortem highlights the challenges of monitoring the response to treatment and illustrates that the resolution of clinical signs does not necessarily equate with a disease cure.

Hepatic ciliated foregut remnants or cysts are congenital abnormalities resulting from retention of embryonic ciliated foregut within the liver. These structures are rarely reported in the human medical literature and have not been reported in the veterinary literature previously, to our knowledge. We describe here a case of an 8-wk-old male French Bulldog with a congenital patent hepatic ciliated foregut remnant resulting in an umbilicobiliary sinus tract. The dog also had concurrent gallbladder agenesis. The patient had yellow fluid discharging from the umbilicus, mimicking a patent urachus. Surgical exploration, removal, and histology provided a conclusive diagnosis of a hepatic foregut remnant and therapeutic resolution of the clinical signs. The histologic appearance of a hepatic foregut remnant is classical, namely a duct composed of 4 layers: an inner ciliated epithelial lining, loose connective tissue, smooth muscle, and a fibrous capsule.