Pathology of Aging in NODscidgamma Female Mice

Abstract

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.

PCR Prevalence of Murine Opportunistic Microbes and their Mitigation by Using Vaporized Hydrogen Peroxide

“…These findings extend prior reports regarding the utility of PCR testing of IVC exhaust airways as a component of murine health surveillance 2,12,24,31,39,44,45 and are especially applicable to improved health monitoring of immunodeficient mice, in which such agents serve as opportunistic pathogens. 1,5,15,20,56,58,59,74 Although sanitization by mechanized washing reduced the PCR evidence of these microbes, most species (that is, 5 of the 8 obtained) remained PCR-detectable. VHP exposure with equipment left unassembled (that is, in the static-open configuration) did not substantively further reduce the PCR evidence of microbes in exhaust plenums.…”

“…As immunodeficient and genetically engineered mice comprise an ever larger portion of murine inventories, microbes to be monitored in murine facilities will likely expand to include opportunistic microbes, members of the microbiome, and new, previously unrecognized microbial pathogens. 1,5,6,11,15,[18][19][20]39,40,43,46,56,[58][59][60]62,63,74 We recently demonstrated that active-closed VHP sterilization of secondary housing equipment was an important component to facilitywide eradication of Corynebacterium bovis, 43 perhaps one of the more problematic opportunistic outbreaks in an immunodeficient murine colony. Our prior report described that despite the absence of marked, widespread morbidity attributable to Corynebacterium bovis, this organism can be harbored by a number of immunodeficient strains, is PCR-identifiable among unaffected immunocompetent strains, and is broadly disseminated to all facility areas during an outbreak.…”

“…and Klebsiella oxytoca can cause nephritis, 15 and the opportunist Pasteurella pneumotropica may cause pneumonia in aged NSG mice. 59 In addition, the murine skin commensal Staphylococcus xylosus can cause dermatitis, abscess formation, or cystitis in immunodeficient strains, 1,5,20,56,58 and the opportunist Corynebacterium bovis causes hyperkeratotic acanthotic dermatitis in nude mice 11 and skin disease in haired Pkrdc scid mice 60 and hairless immunocompetent SKH1-Hr hr mice 19 and becomes disseminated facilitywide. 6,43 Moreover, a number of microbes either harbored by humans or common to the environment are opportunistic pathogens in immunodeficient mice, including Pseudomonas aeruginosa, β-hemolytic Streptococcus spp., Staphylococcus aureus, and Pneumocystis carinii.…”

Effects of Corynebacterium bovis on Engraftment of Patient-derived Chronic-Myelomonocytic Leukemia Cells in NSGS Mice

“…Immunodeficient mice are exquisitely sensitive to opportunistic microbes, including members of the microbiome and emerging pathogens. 7,25,26,29 In addition to the obvious potential for morbidity or mortality, one detrimental drawback of even subclinical infections of immunodefi cient mice is the variability induced into research data, normative physiologic responses, and to study metrics, thereby invalidating the fi ndings. 25 When murine studies involve rare, genetically unique human PDX specimens and when experimental therapeutics are available only in limited aliquots, the tolerance for data variability and study invalidation due to opportunistic microbes becomes substantially less.…”

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

“…Pneumocystis murina: respiratory disease and mortality in immunodeficient mice. 378,381,[534][535][536] Candida spp. : recent reports associated with immune deficiency/suppression and or use of antimicrobials.…”