Viral Vector Biosafety in Laboratory Animal Research.

Viral vector research presents unique occupational health and safety challenges to institutions due to the rapid development of both in vivo and in vitro gene-editing technologies. Risks to human and animal health make it incumbent on institutions to appropriately evaluate viral vector usage in research on the basis of available information and governmental regulations and guidelines. Here we review the factors related to risk assessment regarding viral vector usage in animals and the relevant regulatory documents associated with this research, and we highlight the most commonly used viral vectors in research today. This review is particularly focused on the background, use in research and associated health and environmental risks related to adenoviral, adeno-associated viral, lentiviral, and herpesviral vectors.

Renal transitional cell carcinoma and choristoma in a degu (Octodon degus).

A 4.5-year-old female degu (Octodon degus) was minimally responsive with a poor body condition, a rough haircoat, and moderate dehydration. Blood was present around its urethral orifice and on the cage bedding. Laboratory analyses revealed leukocytosis with neutrophilia and anemia; hypoproteinemia and hypoalbuminemia; hyperglycemia, hyperphosphatemia, and elevated alanine aminotransferase, blood urea nitrogen, and creatinine; and hematuria and pyuria with occasional squamous and transitional epithelial cells. A urine culture was positive for coagulase-negative Staphylococcus sp. On gross necropsy, the right kidney was enlarged, cystic, and greenish-brown, with a 10-mm, hemorrhagic, granular mass extending from the renal pelvis into the cranial cortex. Only a small amount of renal cortex appeared normal. The urinary bladder had focal areas of hemorrhage and contained frank blood. Histologically, the papillary mass in the right renal pelvis comprised basophilic, moderately anaplastic, clustered epithelial transition cells consistent with a transitional cell carcinoma. Internally, the tumor showed squamous metaplasia and moderate multifocal interstitial fibrosis. The right kidney cortex contained a choristoma comprising trabecular bone, mature adipocytes, and cellular infiltrates suggestive of osteocytes, lymphocytes, and plasma cells. The urinary bladder had mild to moderate, focal, hemorrhage with neutrophilic inflammation and contained focal areas of mild transitional cell epithelial hyperplasia; these changes may have been secondary to irritation by hemorrhage in the renal pelvis. There was no evidence of metastasis. Renal transitional cell tumors are rare in rodents. This is the first report of both a renal transitional cell carcinoma and a renal choristoma in a degu.

Quantification of TNF-alpha and IL-6 bioactivity in response to lipopolysaccharide in the degu (Octodon degus).

The proinflammatory cytokines TNF-alpha and IL-6 are important inflammatory mediators that may be regulated by circadian rhythms. However, the production and detection of these cytokines have not been examined in the degu, a diurnal species used in some studies of circadian rhythms. In this study, we used bioassays to attempt to measure tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) levels in degus exposed to an inflammatory stimulus, lipopolysaccharide (LPS). In an in vitro study, whole blood was incubated with LPS. After 6 and 24 h of LPS stimulation, TNF-alpha levels were substantially increased. However, IL-6 was not found in any of the samples. In an in vivo study, LPS was given to degus intraperitoneally. Similar to responses seen in other species, LPS stimulation resulted in marked neutrophil recruitment into the peritoneal space but not the alveolar space. TNF-alpha was present in large amounts in plasma and/or peritoneal lavage fluid. Again, IL-6 was not detectable with the bioassay. These findings suggest that degus do not produce IL-6, that they produce IL-6 in extremely small amounts, or that the bioassay is unable to detect IL-6 from degus. In conclusion, using well-established models of acute inflammation, this study demonstrated that TNF-alpha, but not IL-6, could be detected in plasma and peritoneal lavage fluids from degus with standard bioassays used for cytokine detection in other species.

Polycystic and chronic kidney disease in a young degu (Octodon degus).

A young adult (approximately 20 months), 125 g, female degu (Octodon degus) was housed with a male degu for approximately 1.2 years as a breeding pair. The female was multiparous and had weaned its third litter 2 weeks earlier. The degu was reported to the veterinary service for bloody vaginal discharge and a hunched, thin appearance of 1 day's duration. On physical examination, it exhibited cachexia, molting, slight matting of the hair around the eyes, and moderate dehydration. Hematology results included anemia and leukopenia with lymphocytopenia. Biochemical abnormalities included severe azotemia and phosphatemia. Urine specific gravity was 1.016. The condition of this animal prohibited its continued use in the breeding colony, so it was submitted for necropsy. On gross examination, the left kidney measured 10 x 15 mm, had an irregular surface, and was pale and mildly enlarged, consistent with compensatory hypertrophy. The right kidney was small (5 x 8 mm) and cystic. Both adrenal glands appeared mildly enlarged. Histologically, the left kidney had multiple regions with chronic, diffuse interstitial nephritis, and the right kidney was polycystic. There was mild, focal, cortical nodular hyperplasia in the adrenal glands. In the uterus, there was unilateral, locally extensive necrosis of the endometrium. The clinical chemistry results and histopathology findings are supportive of a diagnosis of renal failure secondary to chronic nephritis and polycystic kidney disease. The etiology of the nephritis is unknown. Polycystic kidney disease can be congenital or hereditary in other rodents.