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Mrl mice

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MRL+/+ mice are a strain of laboratory mice that are genetically modified. They are commonly used in research to study autoimmune disorders and other immunological conditions. The core function of these mice is to serve as a model for such research purposes.

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8 protocols using mrl mice

1

BaP-induced Lupus in MRL Mice

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MRL mice were purchased from the Jackson Laboratory and subjected to BaP treatment over the course of 8 weeks, starting at 8 weeks of age, following established procedures [13 (link),14 (link),38 (link),39 (link)]. Mouse body weight was monitored biweekly, and white blood cell count was performed at week 4 and week 8 of treatment. Plasma was collected for a-dsDNA level by ELISA, and urine was collected for proteinuria analysis at 6 weeks. At the end of the treatment, terminal blood collection was performed, and tissues were snap-frozen for RNA analysis, OCT-embedded for immunofluorescence analysis, and formalin-fixed and embedded for H&E staining and spatial transcriptomic analysis. All animal experiments were conducted with IACUC approval.
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2

Autoimmune Triggers in MRL+/+ Mice

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Female MRL+/+ mice were selected for this study. Autoimmune disease in humans is known to involve an ill-defined genetic predisposition, and is most often found in women. Young adult female MRL+/+ mice, with a propensity for autoimmunity but absence of overt disease, can be used to mimic these requirements, and are used to test for the ability of different toxicants to trigger or augment autoimmunity as previously described [38 (link)]. Eight week-old female MRL+/+ mice (Jackson Laboratories; Bar Harbor, ME, USA) were housed in polycarbonate ventilated cages and provided with lab chow (Harlan 7027) and drinking water ad libitum. TCE (purity 99+%; Aldrich Chemical Co. Inc.; Milwaukee, WI, USA) was suspended in drinking water with 1% emulsifier Alkamuls EL-620 from Rhone-Poulenc (Cranbury, NJ). The mice (8–9 mice/group) received either 0 or 0.5 mg/ml TCE in their drinking water for 40 weeks. Freshly made TCE-containing drinking water was provided every 3–4 days. The mice were weighed once a month. On the basis of water intake, body weight and measured TCE degradation in the water bottles the mice were exposed to an average of 40–50 mg/kg/day TCE. This does is occupationally relevant based on the current 8-h Permissible Exposure Limit [established by the Occupational Safety and Health Administration (OSHA)] for TCE is 100ppm or ∼76 mg/kg/day.
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3

Toxicological Effects of TCE and NAC

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Five-week old female MRL+/+ mice (23–26 g) were purchased from The Jackson Laboratory (Bar Harbor, ME) and housed at the UTMB animal house facility maintained at ∼22°C, 50–60% relative humidity, and a 12 hr light/dark cycle. The animals were provided standard lab chow and drinking water ad libitum and were acclimated for 1 week prior to the treatment. The experiments were performed in accordance with the guidelines of the National Institutes of Health and were approved by the Institutional Animal Care and Use Committee of University of Texas Medical Branch. The mice, divided into 4 groups of 6 each, were treated with TCE, NAC or TCE plus NAC (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water) [3] (link), [21] (link), [25] (link),[32] (link),. The control mice received an equal volume of corn oil only. After 6 weeks of treatment, the animals were euthanized under nembutal (sodium pentobarbital) anesthesia, and blood was withdrawn from the inferior vena cava. Individual sera, obtained following blood clotting and centrifugation, were stored in small aliquots at −80°C until further analysis. At the same time, major organs were immediately removed and weighed. Portions of livers and kidneys from control and TCE-treated mice were snap-frozen in liquid nitrogen and stored at −80°C for the further analysis.
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4

Chronic TCE Exposure in MRL+/+ Mice

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Eight week-old female MRL+/+ mice (Jackson Laboratories; Bar Harbor, ME) were exposed to TCE as previously described.(15 (link)) The mice (8–9 mice/treatment group/time point) received 0 or 0.5 mg/ml TCE in their drinking water for 4, 10, 16, 22, 28, 34 or 40 weeks. Mice received drinking water and food (Harlan 7027) ad libitum. TCE exposure from water consumption averaged 40–50 mg/kg/day, in comparison to the Permissible Exposure Limit [established by the Occupational Safety and Health Administration (OSHA)] for TCE of approximately 76 mg/kg/day. All studies were approved by the Animal Care and Use Committee at the University of Arkansas for Medical Sciences.
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5

Transgenerational Effects of TCE and HFD

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As shown in Figure 1, beginning at 4 weeks of age, female MRL+/+ mice (Jackson Laboratories; Bar Harbor, ME) to be used as breeding dams were randomly assigned to one of four exposure groups as described.42 (link) The four experimental groups consisted of: 1) mice receiving vehicle control drinking water and 10% kcal fat diet or “control” mice (TCE/HFD); 2) mice receiving vehicle control drinking water and 40% kcal fat diet or “HFD” (TCE/HFD+); 3) mice receiving TCE in the drinking water and 10% kcal fat diet or “TCE” (TCE+/HFD); 4) mice receiving TCE in the drinking water and 40% kcal fat diet or “co-exposed” (TCE+/HFD+). The female dams were mated with previously untreated male MRL+/+ mice. The TCE was administered (0 or 0.05 μg/ml) in drinking water as previously described.43 (link) At weaning [postnatal day (PND) 21] the male pups were separated from females and group housed according to their exposure for the duration of the experiment.
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6

Murine Model of Systemic Lupus

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Experiments involving animals were reviewed and approved by the Animal Care and Use Committees from the Universities of Chicago and Buffalo (MED09122Y and PROTO201800154), and were performed in compliance with current animal use guidelines. Mice used in this study were maintained under pathogen-free conditions with a 12-hour light and dark cycle. Male congenic control MRL+/+ mice and MRL/lpr lupus mice (6–8 weeks) were purchased from the Jackson Laboratory and maintained in our facility.
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7

Autoimmune Disease Induction in MRL+/+ Mice

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Female MRL+/+ mice were selected for this study. Autoimmune disease in humans is known to involve an ill-defined genetic predisposition, and is most often found in women. Young adult female MRL+/+ mice, with a propensity for autoimmunity but absence of overt disease, can be used to mimic these requirements, and are used to test for the ability of different toxicants to trigger or augment autoimmunity as previously described [38 (link)]. Eight week-old female MRL+/+ mice (Jackson Laboratories; Bar Harbor, ME, USA) were housed in polycarbonate ventilated cages and provided with lab chow (Harlan 7027) and drinking water ad libitum. TCE (purity 99+ %; Aldrich Chemical Co. Inc.; Milwaukee, WI, USA) was suspended in drinking water with 1% emulsifier Alkamuls EL-620 from Rhone-Poulenc (Cranbury, NJ). The mice (8–9 mice/group) received either 0 or 0.5 mg/ml TCE in their drinking water for 40 weeks. Freshly made TCE-containing drinking water was provided every 3–4 days. The mice were weighed once a month. On the basis of water intake, body weight and measured TCE degradation in the water bottles the mice were exposed to an average of 40–50 mg/kg/day TCE. This does is occupationally relevant based on the current 8-h Permissible Exposure Limit [established by the Occupational Safety and Health Administration (OSHA)] for TCE is 100 ppm or ∼76 mg/kg/day.
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8

Murine Inflammation Modeling with MRL+/+ Mice

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Five-week old female MRL+/+ mice were purchased from the Jackson Laboratory (Bar Harbor, ME) and maintained under specific pathogen-free facility and acclimatized for one week prior to any treatment. All animal research protocols were approved by the Institutional Animal Care and Use Committee of the University of Texas Medical Branch at Galveston (UTMB). All animal experiments are complied with the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and carried out in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals.
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