Opportunistic Bacterial Infections in Breeding Colonies of the NSG Mouse Strain

Foreman, Oded; Kavirayani, Anoop; Griffey, Stephen M.; Reader, Rachel; Shultz, Leonard D.

doi:10.1177/0300985810378282

Cited by 50 publications

(59 citation statements)

References 18 publications

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“…6 In this study mammary tumors were the most common type of neoplasm, and a common COD. While we are aware of few previous report of mammary neoplasms in NSG mice, 12,61 they were described as a common finding in NOD and NOD-derived strains. 28 Mammary tumors were often accompanied by pulmonary metastases.…”

Section: Discussionmentioning

confidence: 82%

“…28,60 Due to their high level of immunodeficiency, morbidity and mortality caused by opportunistic infections have been reported in NSG mice, even in breeding colonies in maximum level barrier facility by a commercial vendor. 12 …”

mentioning

confidence: 99%

“…Neoplasms including mammary adenocarcinomas, osteosarcomas, and lymphomas were mentioned, and the frequency and age of onset of these conditions were compatible with those in other NOD-derived strains (unpublished data). 12 Despite their reported lifespan of >89 weeks and increasing use in cancer and immune research, no comprehensive description of naturally occurring aged-related lesions of NSG mice has been published. Given the prominent use of this strain in biomedical research, a better understanding of naturally occurring pathology, including spontaneous age-related lesions and natural causes of morbidity and mortality, is required in order to ensure correct interpretation of results in experiments in which this strain is used.…”

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confidence: 99%

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Pathology of Aging in NODscidgamma Female Mice

et al. 2017

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In the past decade, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, NOD scid gamma) mice have become a model of choice in several areas of biomedical research; however, comprehensive data on their spontaneous age-related pathology are not currently available in the literature. The prevalence of spontaneous morbidity affecting aged NSG female breeders enrolled in a parasitology study was documented with classification of neoplastic and non-neoplastic (inflammatory, metabolic, degenerative) lesions. Malignant mammary neoplasms were most commonly diagnosed, often accompanied by pulmonary metastases, while a low frequency of lymphoma and histiocytic sarcoma was documented. The major inflammatory conditions were suppurative pleuropneumonia and bronchopneumonia with abscess formation, from which Pasteurella pneumotropica was commonly isolated, followed by otitis media. Both inflammatory and degenerative lesions of the genital tract were identified, along with neoplasms such as endometrial yolk sac carcinomas and granulosa cell tumors. Novel conditions identified included renal tubular degeneration and necrosis associated with 2 concurrent types of intranuclear inclusions, focal or multifocal hyperostosis of the skull, and neuroendocrine tumors of the mesometrium. The majority of degenerative lesions that affected the genital tract, endocrine, and skeletal systems did not represent the actual underlying cause of death but, rather, were considered incidental findings. This study indicates that both inflammatory and neoplastic conditions contribute to morbidity and mortality in experimentally manipulated aged female NSG mice.

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Section: Discussionmentioning

confidence: 82%

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confidence: 99%

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confidence: 99%

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Pathology of Aging in NODscidgamma Female Mice

et al. 2017

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“…The relationship between these findings and viral infection is under current investigation[34]. These data, taken together, demonstrate nanoART efficacy patterns close to infected ART-treated humans.…”

Section: Discussionmentioning

confidence: 82%

Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1-infected humanized mice

Dash

Gendelman

Roy

et al. 2012

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Objectives Long-acting nanoformulated antiretroviral therapy (nanoART) with improved pharmacokinetics, biodistribution and limited systemic toxicities will likely improve drug compliance and access to viral reservoirs. Design Atazanvir and ritonavir crystalline nanoART were formulated in a poloxamer-188 excipient by high-pressure homogenization. These formulations were evaluated for antiretroviral and neuroprotective activities in humanized NOD/scid-IL-2Rgcnull (NSG) mice. Methods NanoART-treated NSG mice were evaluated for drug biodistribution, pharmacodynamics and nanotoxicology. CD34+ human hematopoietic stem cells were transplantation at birth in NSG mice. The mice were infected with HIV-1ADA at 5 months of age and 8 weeks later, infected animals were treated with weekly subcutaneous injections of nanoformulated ATV and RTV. Peripheral viral load, CD4+ T cell count, lymphoid tissue and brain pathology were evaluated. Results NanoART treatments by 6 once a week injections reduced viral loads >1000 fold and protected CD4+ T cell populations. This paralleled high ART levels in liver, spleen and blood that were in or around the human minimal effective dose concentration without notable toxicities. Importantly, examination of infected brain subregions showed that nanoART elicited neuroprotective responses with detectable increases in microtubule-associated protein-2, synaptophysin and neurofilament expression when compared to untreated virus-infected animals. Therapeutic interruptions produced profound viral rebounds. Conclusions Long-acting nanoART has translational potential with sustained and targeted efficacy and with limited systemic toxicities. Such success in drug delivery and distribution could improve drug adherence and reduce viral resistance in infected people.

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“…Several studies described reduced amounts of complement factors with weak activity in newborns (26)(27)(28)(29), impairing the clearance of bacterial infections. Similarly, there is a lack of human complement as well as dysfunctional mouse complement in humanized mice (30)(31)(32).…”

Section: Il2rgmentioning

confidence: 99%

Humanized Mice, a New Model To Study the Influence of Drug Treatment on Neonatal Sepsis

et al. 2013

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cBacterial infection with group B Streptococcus (GBS) represents a prominent threat to neonates and fetuses in the Western world, causing severe organ damage and even death. To improve current therapeutic strategies and to investigate new approaches, an appropriate in vivo model to study the immune response of a human immune system is needed. Therefore, we introduced humanized mice as a new model for GBS-induced sepsis. Humanized mice feature deficiencies similar to those found in neonates, such as lower immunoglobulin levels and myeloid cell dysfunction. Due to the husbandry in specific-pathogen-free (SPF) facilities, the human immune cells in these mice also exhibit a naive phenotype which mimics the conditions in fetuses/ neonates. Following infection, cytokine release and leukocyte trafficking from the bone marrow to the lymphoid organ (spleen) and into the peritoneum (site of infection) as well as bacterial spreading and clearance were traceable in the humanized mice. Furthermore, we investigated the effects of betamethasone and indomethacin treatment using this novel sepsis model. Although both drugs are commonly used in perinatal care, little is known about their effects on the neonatal immune system. Treatment of infected humanized mice not only induced the reduction of human leukocytes in the spleen but also increased the bacterial load in all analyzed organs, including the brain, which did not show infiltration of live GBS in untreated controls. These studies demonstrate the utility of the humanized mice as a new model to study an immature human immune response during bacterial infection and allow the investigation of side effects induced by various treatments.

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Opportunistic Bacterial Infections in Breeding Colonies of the NSG Mouse Strain

Cited by 50 publications

References 18 publications

Pathology of Aging in NODscidgamma Female Mice

Pathology of Aging in NODscidgamma Female Mice

Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1-infected humanized mice

Humanized Mice, a New Model To Study the Influence of Drug Treatment on Neonatal Sepsis

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