Degenerative Myelopathy and Neuropathy in NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) Mice Caused by Lactate Dehydrogenase–Elevating Virus (LDV)

Abstract

Following implantation of patient-derived xenograft (PDX) breast carcinomas from three separate individuals, 33/51 female NOD. Cg-Prkdc scid Il2rg tm1Wjl/SzJ (NSG) mice presented with progressive, unilateral to bilateral, ascending hindlimb paresis to paralysis. Mice were mildly dehydrated, in thin to poor body condition, with reduced to absent hindlimb withdrawal reflex and deep pain sensation. Microscopically, there was variable axonal swelling, vacuolation, and dilation of myelin sheaths within the ventral spinal cord and spinal nerve roots of the thoracolumbar and sacral spinal cord, as well as within corresponding sciatic nerves. Results of PCR screening of PDX samples obtained at necropsy and pooled environmental swabs from the racks housing affected animals were positive for lactate dehydrogenase–elevating virus (LDV). LDV is transmitted through animal-animal contact or commonly as a contaminant of biologic materials of mouse origin. Infection is associated with progressive degenerative myelopathy and neuropathy in strains of mice harboring endogenous retrovirus (AKR, C58), or in immunosuppressed strains (NOD-SCID, Foxn1nu), and can interfere with normal immune responses and alter engraftment and growth of xenograft tumors in immunosuppressed mice. This is the first reported series of LDV-induced poliomyelitis in NSG mice and should be recognized as a potentially significant confounder to biomedical studies utilizing immunodeficient xenograft models.

Post-Transplant Cyclophosphamide Combined with Brilliant Blue G Reduces Graft-versus-Host Disease without Compromising Graft-versus-Leukaemia Immunity in Humanised Mice

“…The GVL mouse however was found deceased on Day 19 and was excluded from the above and subsequent analyses. Spleens and faeces collected from the other two mice at endpoint were examined for lactate dehydrogenase elevating virus, associated with myelopathy and neuropathy in NSG mice [28], with both mice testing negative for this virus, and thus included in all analyses.…”

Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) Mice

“…These mice are susceptible to a wider range of agents that typically do not infect or cause clinical disease in immunocompetent mice 13 and therefore represent a significant source of confounding in preclinical studies that may lead to misinterpretation of clinical and pathology data. 47,53 Newer immunodeficient mice, such as NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice, have multiple mutations of the immune system which produce profound immune alterations and consequently need additional protections and surveillance to prevent contamination of the environment, exposure of animals to potential pathogens, and loss of animals and research data critical for preclinical studies in biomedical research.…”