Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19.

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers.

Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19.

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a limited range of other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad range of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers.

Targeting canine mammary neoplastic epithelial cells with a reengineered anthrax toxin: first study.

Mammary tumors are the most frequent type of neoplasms in intact female dogs. New therapies that target neoplastic cells without affecting normal cells are highly sought. The Bacillus anthracis toxin has been reengineered to target tumor cells that express urokinase plasminogen activators and metalloproteinases.

Development of a Radiation-induced Pulmonary Fibrosis Partial Body Irradiation Model in C57BL/6 Mice.

With the current volatile geopolitical climate, the threat of nuclear assault is high. Exposure to ionizing radiation from either nuclear incidents or radiological accidents often lead to major harmful consequences to human health. Depending on the absorbed dose, the symptoms of the acute radiation syndrome and delayed effects of acute radiation exposure (DEARE) can appear within hours, weeks to months.

Establishment and Characterization of Amitrole-Induced Mouse Thyroid Adenomatous Nodule-Derived Cell Lines.

Thyroid cancer cell lines have been of great value for the study of thyroid cancer. However, the availability of benign thyroid adenoma cell lines is limited. Cell lines were established from thyroid adenomatous nodules that developed in mice treated with the goitrogen amitrole.

Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 delta and beyond.

Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2 dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus and .

Brain and spinal cord lesions in 28 inbred strains of aging mice.

Brain and spinal cord histopathology findings in male and female 20-month-old mice in a large-scale aging study of 28 inbred Jackson Laboratory mouse strains from 7 genetic families are described. Brain sections from selected strains at 12 and 24 months of age or older were also reviewed. Common lesions include axonal dystrophy in the gracile and/or cuneate nucleus in the sensory tract of the dorsal medulla and in the spinal cord in all strains.

EPCAM and TROP2 share a role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice.

Epithelial cell adhesion molecule (EPCAM) is a transmembrane glycoprotein expressed on the surface of most epithelial and epithelium-derived tumor cells and reported to regulate stability of epithelial tight junction proteins, claudins. Despite its widespread expression, loss of EPCAM function has so far only been reported to prominently affect intestinal development, resulting in severe early onset enteropathy associated with impaired growth and decreased survival in both humans and mice. In this study, we show that the critical role of EPCAM is not limited to intestinal tissues and that it shares its essential function with its only known homolog, Trophoblast cell surface antigen 2 (TROP2).

Scientific and Regulatory Policy Committee Points to Consider: Primary Digital Histopathology Evaluation and Peer Review for Good Laboratory Practice (GLP) Nonclinical Toxicology Studies.

The Society of Toxicologic Pathology's Scientific and Regulatory Policy Committee formed a working group to consider the present and future use of digital pathology in toxicologic pathology in general and specifically its use in primary evaluation and peer review in Good Laboratory Practice (GLP) environments. Digital histopathology systems can save costs by reducing travel, enhancing organizational flexibility, decreasing slide handling, improving collaboration, increasing access to historical images, and improving quality and efficiency through integration with laboratory information management systems. However, the resources to implement and operate a digital pathology system can be significant.

Scientific and Regulatory Policy Committee Brief Communication: 2019 Survey on Use of Digital Histopathology Systems in Nonclinical Toxicology Studies.

Histopathologic evaluation and peer review using digital whole-slide images (WSIs) is a relatively new medium for assessing nonclinical toxicology studies in Good Laboratory Practice (GLP) environments. To better understand the present and future use of digital pathology in nonclinical toxicology studies, the Society of Toxicologic Pathology (STP) formed a working group to survey STP members with the goal of creating recommendations for implementation. The survey was administered in December 2019, immediately before the COVID-19 pandemic, and the results suggested that the use of digital histopathology for routine GLP histopathology assessment was not widespread.

Histology Atlas of the Developing Mouse Placenta.

The use of the mouse as a model organism is common in translational research. This mouse-human similarity holds true for placental development as well. Proper formation of the placenta is vital for development and survival of the maturing embryo.

St. John's Wort alleviates dextran sodium sulfate-induced colitis through pregnane X receptor-dependent NFκB antagonism.

St. John's wort (SJW), from traditional herbs, activates the pregnane X receptor (PXR), a potential drug target for treating inflammatory bowel disease (IBD). However, how SJW alleviates dextran sodium sulfate (DSS)-induced experimental IBD by activating PXR is unknown.

Proceedings of the 2021 National Toxicology Program Satellite Symposium.

The 2021 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was the 20th anniversary of the symposia and held virtually on June 25th, in advance of the Society of Toxicologic Pathology's 40th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were presented to the audience for voting and discussion.

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression.

The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC.

Visualization of Resident Memory CD8 T Cells in the Lungs of Young and Aged Influenza Memory Mice and after Heterosubtypic Challenge.

Memory T cells that are resident in the tissues (T resident memory [Trm]) serve as frontline responders to prevent reinfection by pathogens. Trm in the lung protect against respiratory viruses. Although these cells have been well characterized, little is known about the impact of immune aging on the establishment, maintenance, function and recall of lung-resident Trm in the context of an influenza virus infection.

Investigating the Multifaceted Nature of Radiation-Induced Coagulopathies in a Göttingen Minipig Model of Hematopoietic Acute Radiation Syndrome.

Coagulopathies are well documented after acute radiation exposure at hematopoietic doses, and radiation-induced bleeding is notably one of the two main causes of mortality in the hematopoietic acute radiation syndrome. Despite this, understanding of the mechanisms by which radiation alters hemostasis and induces bleeding is still lacking. Here, male Göttingen minipigs received hematopoietic doses of 60Co gamma irradiation (total body) and coagulopathies were characterized by assessing bleeding, blood cytopenia, fibrin deposition, changes in hemostatic properties, coagulant/anticoagulant enzyme levels, and markers of inflammation, endothelial dysfunction, and barrier integrity to understand if a relationship exists between bleeding, hemostatic defects, bone marrow aplasia, inflammation, endothelial dysfunction and loss of barrier integrity.

Exclusion of Expert Contributors From Authorship Limits the Quality of Scientific Articles.

Veterinary pathologists are key contributors to multidisciplinary biomedical research. However, they are occasionally excluded from authorship in published articles despite their substantial intellectual and data contributions. To better understand the potential origins and implications of this practice, we identified and analyzed 29 scientific publications where the contributing pathologist was excluded as an author.

Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation.

A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor gene mutations driving cellular transformation and tumor progression in the absence of oncogenic driver mutation(s). Multiple in vitro and in vivo gene inactivation screens have enhanced our understanding of the tumor suppressor gene landscape in various cancers. However, these studies are limited to single or combination gene effects, specific organs, or require sensitizing mutations.

Brain Lesions in Aging Zoo-Housed Naked Mole-Rats ().

Naked mole-rats (NMRs) are common in the managed care of zoos and valuable models for aging research. Limited information on NMR neuropathology is available despite many studies regarding their aging physiology. Histologic sections of brain from 27 adult (5-27 years old) NMRs from 2 zoos were reviewed to determine presence or absence of lesions associated with advanced age in humans and other mammals.

Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells.

Canine and human osteosarcomas (OSA) share similarities. Novel therapies are necessary for these tumours. The toxin was reengineered to target and kill cells with high expressions of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA).