Detection of Lactate Dehydrogenase Elevating Virus in a Mouse Vivarium Using an Exhaust Air Dust Health Monitoring Program

Luchins, Kerith R; Mailhiot, Darya; Theriault, Betty; Langan, George

doi:10.30802/aalas-jaalas-19-000107

Cited by 9 publications

(5 citation statements)

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“…Infected mice still shed virus into the environment; however, environmental surveillance via individually ventilated cage (IVC) rack exhaust air dust collection media has been reported to detect the presence of LDV within a given colony. 32 In this study, environmental sampling indicated that only the rack housing LDVinfected animals tested positive while other racks housing NSG and other immunodeficient strains were negative, suggesting LDV is not enzootic in these colonies. Serial passage of PDX tumors is necessary to ensure these samples are stable and can be maintained in recipient mice over time; therefore, rather than contracting the disease from the environment or infected mice as occurs in natural infection, it is thought that infection occurred at some point through the process of passage in recipient animals.…”

Section: Discussionmentioning

confidence: 53%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 53%

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

et al. 2022

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“…Until now, EAD-based monitoring approaches proved to be suitable for a broad variety of infectious agents, such as MNV [ 161 , 167 ], MHV [ 158 ], Murine Astrovirus [ 168 ], Lactate–Dehydrogenase–Elevating–Virus (LDEV) [ 169 ], Rodentibacter sp. [ 153 , 162 ], Helicobacter sp.…”

Section: How To Ensure Qualitymentioning

confidence: 99%

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

Buchheister

Bleich

2021

Animals

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The health monitoring of laboratory rodents is essential for ensuring animal health and standardization in biomedical research. Progress in housing, gnotobiotic derivation, and hygienic monitoring programs led to enormous improvement of the microbiological quality of laboratory animals. While traditional health monitoring and pathogen detection methods still serve as powerful tools for the diagnostics of common animal diseases, molecular methods develop rapidly and not only improve test sensitivities but also allow high throughput analyses of various sample types. Concurrently, to the progress in pathogen detection and elimination, the research community becomes increasingly aware of the striking influence of microbiome compositions in laboratory animals, affecting disease phenotypes and the scientific value of research data. As repeated re-derivation cycles and strict barrier husbandry of laboratory rodents resulted in a limited diversity of the animals’ gut microbiome, future monitoring approaches will have to reform—aiming at enhancing the validity of animal experiments. This review will recapitulate common health monitoring concepts and, moreover, outline strategies and measures on coping with microbiome variation in order to increase reproducibility, replicability and generalizability.

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“…PCR on nucleic acids extracted from filters has proven to be more sensitive and effective than the use of sentinels for the detection of specific pathogens such as Murine norovirus (MNV) (Zorn et al, 2017 ), Mouse hepatitis virus (MHV) (O’Connell et al, 2021 ), Sendai virus (Compton et al, 2004b ), Murine Astrovirus (Korner et al, 2019 ), Pasteurella pneumotropica (Miller et al, 2016 ), Helicobacter spp. (Mailhiot et al, 2020 ), Lactate dehydrogenase elevating virus (LDV) (Luchins et al, 2020b ), Pneumocystis murina (Miller and Brielmeier, 2018 ), fur mites (Hanson et al, 2021 ) ( Gerwin et al, 2017 ) ( Korner et al, 2019 ) Protozoa and pinworm (Kapoor et al, 2017 ) (Dubelko et al 2018 ) (Bauer et al, 2016 ). This rodent-free approach is ethical reducing animals and animal manipulations.…”

Section: Introductionmentioning

confidence: 99%

Microbiota and environmental health monitoring of mouse colonies by metagenomic shotgun sequencing

Lupini

Bassi

Guerriero

et al. 2022

World J Microbiol Biotechnol

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Metagenomic next-generation sequencing (mNGS) allows the monitoring of microbiota composition of murine colonies employed for scientific purposes in a single test by assessing the composition of gut microbiome and the detection of pathogens from fecal pellets. In this study, we tested the potential use of mNGS for monitoring both microbiota composition and the presence of pathogens through Environmental Health Monitoring, by using exhaust dust collection filters derived from individually ventilated cages (IVC) systems.mNGS analysis was performed on nucleic acids isolated from filters collecting air from the exhaust of: (1) cages with mice housed in a non-pathogen free facility; (2) animal-free cages with clean chow and bedding from the same facility; (3) cages housing mice from a specific-pathogen free (SPF) facility. mNGS results revealed correspondence between microbiome composition from fecal pellets and filter, including pathogenic bacteria (Helicobacter hepaticus, Helicobacter typhlonius, Chlamydia muridarum, Rodentibacter pneumotropicus, Citrobacter rodentium), intestinal protozoa (Tritrichomonas muris, Spironucleus muris) nematoda (Aspiculuris tetraptera) and eukaryotic parasites (Myocoptes musculinus), present in the colony. Entamoeba muris and Syphacia obvelata were detected in fecal pellets but not in filter. The animal free exhaust dust filter, exposed to clean cages (no mice) placed in the IVC after removal of all mice, exhibited the presence of the same pathogens due to contaminated connecting pipes, confirming the sensitivity of the approach. Conversely, the filter from SPF colony revealed the absence of pathogens.The current use of exhaust dust collection filters in health surveillance requires multiple molecular tests to identify specific pathogens and does not provide information on the colony microbiome. This work provides the proof-of-principle that assaying exhaust dust collection filters by mNGS for microbiota monitoring of laboratory mice is feasible. In its daily application, results suggest the usefulness of the test in SPF facilities, where pathogenic micro-organisms are expected to be absent. mNGS analysis of exhaust dust collection filters allows the analysis of multiple cages, reducing the number of tests required for pathogen detection and corresponding costs, and avoiding the use of sentinel mice.

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Detection of Lactate Dehydrogenase Elevating Virus in a Mouse Vivarium Using an Exhaust Air Dust Health Monitoring Program

Cited by 9 publications

References 10 publications

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

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

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

Microbiota and environmental health monitoring of mouse colonies by metagenomic shotgun sequencing

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Detection of Lactate Dehydrogenase Elevating Virus in a Mouse Vivarium Using an Exhaust Air Dust Health Monitoring Program

Cited by 9 publications

References 10 publications

Degenerative Myelopathy and Neuropathy in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) Mice Caused by Lactate Dehydrogenase–Elevating Virus (LDV)

Degenerative Myelopathy and Neuropathy in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) Mice Caused by Lactate Dehydrogenase–Elevating Virus (LDV)

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

Microbiota and environmental health monitoring of mouse colonies by metagenomic shotgun sequencing

Contact Info

Product

Resources

About

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

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