Immunodeficient and Humanized Mice

Santagostino, Sara Francesca; Monette, Sébastien; Piersigilli, Alessandra; Godfrey, Virginia; HogenEsch, Harm

doi:10.1002/9781119624608.ch9

Cited by 2 publications

(2 citation statements)

References 126 publications

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“…NOD.SCID mice were utilized as while they are immunocompromised, however they are less immunodeficient than NSG mice. 61 C and B6 mice were treated with TMS Diet for 7 days while the immunocompromised NOD.SCID mice were treated for 21 days ( TMS Diet-L ). At the end of the treatment period, mice were provided base feed.…”

Section: Methodsmentioning

confidence: 99%

Assessment of Antimicrobial Therapy in EradicatingChlamydia muridarumin Research Mice: Immune Status and its Impact on Outcomes

Palillo,

Carrasco,

Mishkin

et al. 2024

Preprint

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Chlamydia muridarum (Cm) is a moderately prevalent, gram-negative, intracellular bacterium that affects laboratory mice, causing subclinical to severe disease, depending on the host’s immune status. The effectiveness of various antibiotic regimens aimed at eradicating Cm in both immunodeficient and immunocompetent laboratory mice was evaluated. NSG mice were cohoused with Cm-shedding BALB/cJ mice for 14 days to simulate natural exposure. Four groups of 8 infected NSG mice were treated for 7 days with either 0.08% sulfamethoxazole and 0.016% trimethoprim (TMS) in water, 0.0625% doxycycline in feed, 0.124%/0.025% TMS in feed, or 0.12% amoxicillin in feed. A control group was provided standard water and feed. The impact of treatment on gastrointestinal microbiota (GM) was performed through shotgun sequencing on the last day of treatment. TMS and Amoxicillin had negligible effects on GM, while doxycycline had the largest effect. All antibiotic treated NSG mice exhibited clinical disease, including dehydration, hunched posture, >20% weight loss, and dyspnea, leading to euthanasia 21-40 days post-treatment (32.6 ± 4.2 days; mean ± SD). Untreated controls were euthanized 14-33 days post-exposure (23.75 ± 5.9 days). All mice were fecal PCR positive for Cm at euthanasia. Histological evaluation revealed multifocal histiocytic and neutrophilic bronchointerstitial pneumonia and/or bronchiolitis featuring prominent intralesional chlamydial inclusion bodies in all mice. Subsequently, groups of 8 C57BL/6J, BALB/cJ, NOD.SCID, and NSG mice infected with Cm were treated with 0.124%/0.025% TMS in feed for 7 (BALB/cJ and C57BL/6J) or 21 days (NSG and NOD.SCID). All immunocompetent and NOD.SCID mice were negative for Cm by PCR 14 days post-treatment, remained clinically normal and had no evidence of Cm infection at necropsy, all NSG mice remained Cm positive and were euthanized. While these findings highlight the difficulties in eradicating Cm from highly immunodeficient mice, eradication of Cm from immunocompetent or moderately immunocompromised mice with antibiotics is feasible.

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Section: Methodsmentioning

confidence: 99%

Assessment of Antimicrobial Therapy in EradicatingChlamydia muridarumin Research Mice: Immune Status and its Impact on Outcomes

Palillo,

Carrasco,

Mishkin

et al. 2024

Preprint

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“…Immunodeficient mice used in xenograft studies, such as NOD.Cg‐ Prkdc scid Il2rg tm1Wjl /SzJ (NOD scid gamma, NSG) mice, may develop immunodeficiency‐related pathology that mimics a successfully engrafted human tumor. NSG mice may develop B‐cell lymphomas following inoculation, secondary to expansion of patient‐derived Epstein‐Barr virus (EBV)‐infected lymphocytes, and may spontaneously develop T‐lymphoblastic lymphoma and certain infections (Santagostino et al., 2022; Tillman et al., 2020). Histopathologic confirmation of xenografted tumor material is, therefore, essential to confirm successful engraftment.…”

Section: Image Content and Interpretationmentioning

confidence: 99%

A Primer for Research Scientists on Assessing Mouse Gross and Histopathology Images in the Biomedical Literature

Gifford

2023

Current Protocols

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Advances in genomic technologies have enabled the development of abundant mouse models of human disease, requiring accurate phenotyping to elucidate the consequences of genetic manipulation. Anatomic pathology, an important component of the mouse phenotyping pipeline, is ideally performed by human or veterinary pathologists; however, due to insufficient numbers of pathologists qualified to assess these mouse models morphologically, research scientists may perform “do‐it‐yourself” pathology, resulting in diagnostic error. In the biomedical literature, pathology data is commonly presented as images of tissue sections, stained with either hematoxylin and eosin or antibodies via immunohistochemistry, accompanied by a figure legend. Data presented in such images and figure legends may contain inaccuracies. Furthermore, there is limited guidance for non‐pathologist research scientists concerning the elements required in an ideal pathology image and figure legend in a research publication. In this overview, the components of an ideal pathology image and figure legend are outlined and comprise image quality, image composition, and image interpretation. Background knowledge is important for producing accurate pathology images and critically assessing these images in the literature. This foundational knowledge includes understanding relevant human and mouse anatomy and histology and, for cancer researchers, an understanding of human and mouse tumor classification and morphology, mouse stain background lesions, and tissue processing artifacts. Accurate interpretation of immunohistochemistry is also vitally important and is detailed with emphasis on the requirement for tissue controls and the distribution, intensity, and intracellular location of staining. Common pitfalls in immunohistochemistry interpretation are outlined, and a checklist of questions is provided by which any pathology image may be critically examined. Collaboration with pathologist colleagues is encouraged. This overview aims to equip researchers to critically assess the quality and accuracy of pathology images in the literature to improve the reliability and reproducibility of published pathology data. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

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Immunodeficient and Humanized Mice

Cited by 2 publications

References 126 publications

Assessment of Antimicrobial Therapy in EradicatingChlamydia muridarumin Research Mice: Immune Status and its Impact on Outcomes

Assessment of Antimicrobial Therapy in EradicatingChlamydia muridarumin Research Mice: Immune Status and its Impact on Outcomes

A Primer for Research Scientists on Assessing Mouse Gross and Histopathology Images in the Biomedical Literature

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