Weight changes of SCID mice inoculated with C. burnetii (solid circles) and PBS (open circles). Humanized mouse model is defined as immunodeficient mice engrafting functional human cells and tissues (Walsh et al., 2017).Generally, the humanized mouse model is reconstituted with human blood derived CD34 + stem cells from cord blood (CB), bone marrow (BM), and peripheral blood (PB) (Mosier et al., 1988; Lapidot et al., 1992; Shultz et al., 1995). Immunocytochemistry of the lung (top), liver (middle), and spleen (bottom) of SCID mouse infected with C. burnetii. The C.B-17 scid spontaneous mutant model was derived by embryo transfer in 1989 and rederived in 1998 using donor females from the laboratory of Dr. Mel Bosma of the Fox Chase Cancer Center. Nevertheless, the hearts of SCID mice infected with C. burnetii share some characteristics with the hearts of humans with Q fever endocarditis: focal calcification and large macrophages containing C. burnetii organisms (22). The A/J strain of mice, which is immunocompetent, is the strain that is most susceptible to C. burnetii (25). Heart disease developed in the SCID mouse within 2 months, whereas human chronic Q fever may take years to develop. The finding that hepatosplenomegaly was proportional to the survival period suggests that C. burnetii continued to proliferate in the bodies of the SCID mice. Heart (A and B) and kidney (C) sections from SCID mouse infected with C. burnetii. The lungs, spleen, and liver, which are the general target organs of C. burnetii in experimental animals, had severe lesions and many C. burnetii organisms. SCID mice are routinely used as model organisms for research into the basic biology of the immune system, cell transplantation strategies, and the effects of disease on mammalian systems. CAS PubMed Google Scholar The survival period was 33 ± 2.5 days. (B) C. burnetii antigens were detected as brown granules (arrowheads). The hearts had severe infiltration of vacuolated macrophages in the epicardium and endocardium, including the valvular part. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/gamma(c)(null) mice, cytokine production of spleen cells stimulated with Listeria monocytogenes antigens was compared among … (2005) performed transmission experiments on HBV. To compare the dose responses of the immunodeficient and immunocompetent mice, SCID mice (n = 6) were inoculated intraperitoneally with 0.5 ml of serial 10-fold dilutions (104 to 10−5 TCID50) of C. burnetii. Inoculation of mice and clinical studies. The livers and spleens of the mice were PCR positive. In the lungs, cells accumulated in intra-alveolar septi, stroma adjacent to airways, or venules (Fig. To translate these ex vivo observations into preclinical in vivo studies, we have developed a mouse model of UC, which is based on immune-compromised NOD/Scid IL2Rγ null (NSG) mice reconstituted with peripheral blood mononuclear cells (PBMCs) from UC patients (NSG-UC). However, the immune state of an immunosuppressed animal is unstable, which makes it difficult to study immune reactions. BALB/c mice that were physiologically immunosuppressed by repeated pregnancy for 2 years after C. burnetii infection (28) developed endocarditis with fibrin deposits, a generic sign of chronic lesions, but the incidence of endocarditis was low (2 out of 13 mice). No C. burnetii-specific antibodies or C. burnetii DNA was detected in the control mice. The mice were observed for 37 days, which is the time at which the last C. burnetii-infected mouse died. These results suggest that NOD/SCID/gamma(c)(null) mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. In the present study, we compared the clinical symptoms, the histopathology, and the survival rates of C. burnetii infection in SCID mice and immunocompetent mice to determine whether the SCID mouse could be used as an animal model for chronic Q fever. At necropsy, the spleen and liver were weighed, and a part of each organ was stored at −80°C. We concluded that the deaths of the SCID mice were due to chronic disease, as we observed that the survivability or death of mice infected with C. burnetii is determined within 2 weeks postinfection (references 3 and 25 and our unpublished data). ABC method; magnification, ×200. The LD 50 of C. burnetii in the SCID mice was at least 10 8 times less than that in the C.B-17 mice, none of which died after C. burnetii infection in this study. Acute Q fever is a flu-like illness which is self-limiting and easily treated with antibiotics when an appropriate diagnosis is made. Body weight continued to decline until death (Fig. Hepatosplenomegaly was prominent in the SCID mice (Table 1), and the spleen had a pale color while the liver had necrotic foci. An appropriate experimental animal model for Q fever endocarditis does not yet exist. The LD50 of C. burnetii in the SCID mice was at least 108 times less than that in the C.B-17 mice, none of which died after C. burnetii infection in this study. In the kidney, the glomeruli were typically infiltrated with vacuolated macrophages (Fig. Immunosuppressive treatments of various experimental animals have been reported to raise their susceptibility to C. burnetii (1, 11, 26, 27). NSG™ mouse model variants are the most highly immunodeficient mice and the models of choice for cancer xenograft modeling, stem cell biology, humanized mice, and infectious disease research. As controls, SCID mice (n = 10), C.B-17 mice (n = 6), and A/J mice (n = 6) were mock inoculated with PBS. Our present results reinforce the hypothesis that an immunocompromised state is an important factor in Q fever endocarditis (19). The SCID mouse has a clear and stable immunodeficient state, so it can be an animal model for the study of Q fever in an immunodeficient host. In the mice infected with 10 TCID50 of C. burnetii, the antibody titers to phase I and II C. burnetii ranged from 1:256 to 1:1,024 and from 1:512 to 1:1,024, respectively, and were equivalent in the two mouse strains. C. burnetii organisms were also present within the hepatocytes (Fig. They have been extensively used as hosts for normal and malignant tissue transplants. The uPA/ SCID mouse is a useful model for HCV and HBV infection. 131:490, 1992) to determine whether the mice were infected. The SCID-hu mouse: a small animal model for HIV infection and pathogenesis. However, the SCID mouse model suggests that there is a risk of renal disease associated with C. burnetii infection in immunocompromised hosts. AL, alveolus. The spleen and liver did not retain their original structures due to bursting with macrophages and numerous vacuoles, which were probably the remains of necrotic cells. This is the first report of persistent C. burnetii infection in an animal that resulted in severe chronic lesions and death. The SCID mice had severe chronic lesions. Hematoxylin and eosin staining; magnification, ×200. However, the pathogenesis of renal disease in SCID mice may be different from that in human Q fever cases, because renal disease in human Q fever is due to immune complexes, while the SCID mouse is unable to produce immunoglobulins. Liver and spleen weights in mice inoculated with 10 TCID50 of C. burnetii or PBS.