Different Strains Of Mice Research Articles

IDH1 MUTATIONS AS A IMMUNOTHERAPEUTIC TARGET FOR BRAIN TUMORS

BACKGROUND: Immunotherapy promises an exquisitely precise therapeutic approach, and substantial evidence suggests that activated T cells can eradicate large tumors, even within the “immunologically privileged” brain. EGFRvIII and isocitrate dehydrogenase 1 (IDH1) mutations are two of the only consistent tumor-specific mutations that have been described. IDH1 is an evolutionarily-conserved enzyme essential to cell function. Greater than 90% of all IDH1 mutations occur from a substitution of histidine for arginine at codon 132, resulting in the highly conserved and tumor-specific mutation, IDH1R132H. IDH1R132H is homogeneously expressed in all tumor cells in tumors that express this mutation, including single infiltrating tumor cells but is absent in normal cells. The high frequency, specificity, and homogeneous expression of the IDH1 mutation make it an ideal target for therapeutic intervention. METHODS: To assess IDH1R132H as an immunotherapeutic target, we have developed a series of peptides of various lengths that span the IDH1R123H mutation and that are homologous in mice and humans. The murine homologue of IDH1R123H was cloned and transfected into murine glioma lines to be used as a therapeutic target. For immunogenicity experiments mice received 3 weekly intradermal immunizations with 100 µg of peptide. One week following the third vaccination spleen cells were analyzed for interferon gamma (IFN-γ) production by ELISPOT. Adjuvants investigated included CFA/IFA/IFA, IFA x3, IFA + GM-CSF, and IFA x3 following pretreatment with Imiquimod. For efficacy experiments C57BL/6 mice received three i.d. vaccinations with PEPIDH1M in IFA every seven days or no treatment. Seven days after the third vaccination, mice received IC implantation of 5x104 IDH1R132H positive KR158B tumor cells. RESULTS: Lymphocytes from mice immunized with peptides of various lengths containing the IDH1R123H mutation produced IFN-γ by ELISPOT in response to stimulation with the mutant peptide, PEPIDH1M but not wild type. This was true for four different strains of mice and transgenic HLA-A2 mice. The 25mer PEPIDH1M induced the most robust immune response. Lymphocytes derived from PEPIDH1M immunized mice co-cultured with IDH1R132H positive glioma secrete significantly higher levels of IFN-γ than lymphocytes co-cultured with IDH1R132H negative tumor cells. Mice immunized with the 25mer PEPIDH1M mixed with GM-CSF or after treating the skin site with Imiquimod produce a greater IFN-γ response to PEPIDH1M alone. Mice immunized with 25mer PEPIDH1M and challenged 7 days later with KR158B-IDH1R132H tumors showed a statically significant increase in median survival (P = 0.0385, Wilcoxon). CONCLUSIONS: The 25mer PEPIDH1M is capable of inducing a therapeutically effective immune response against intracranial tumors. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.

Inhibitor(s) of the classical complement pathway in mouse serum limit the utility of mice as experimental models of neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system in which anti-aquaporin-4 (AQP4) autoantibodies (AQP4-IgG) cause damage to astrocytes by complement-dependent cytotoxicity (CDC). Various approaches have been attempted to produce NMO lesions in rodents, some involving genetically modified mice with altered immune cell function. Here, we found that mouse serum strongly inhibits complement from multiple species, preventing AQP4-IgG-dependent CDC. Effects of mouse serum on complement activation were tested in CDC assays in which AQP4-expressing cells were incubated with AQP4-IgG and complement from different species. Biochemical assays and mass spectrometry were used to characterize complement inhibitor(s) in mouse serum. Sera from different strains of mice produced almost no AQP4-IgG-dependent CDC compared with human, rat and guinea pig sera. Remarkably, addition of mouse serum prevented AQP4-IgG-dependent CDC caused by human, rat or guinea pig serum, with 50% inhibition at <5% mouse serum. Hemolysis assays indicated that the inhibitor(s) in mouse serum target the classical and not the alternative complement pathway. We found that the complement inhibitor(s) in mouse serum were contained in a serum fraction purified with protein-A resin; however, the inhibitor was not IgG as determined using serum from IgG-deficient mice. Mass spectrometry on the protein A-purified fraction produced several inhibitor candidates. The low intrinsic complement activity of mouse serum and the presence of complement inhibitor(s) limit the utility of mouse models to study disorders, such as NMO, involving the classical complement pathway.

Immobility responses between mouse strains correlate with distinct hippocampal serotonin transporter protein expression and function.

Mouse strain differences in immobility and in sensitivity to antidepressants have been observed in the forced swimming test (FST) and the tail suspension test (TST). However, the neurotransmitter systems and neural substrates that contribute to these differences remain unknown. To investigate the role of the hippocampal serotonin transporter (5-HTT), we measured baseline immobility and the immobility responses to fluoxetine (FLX) in the FST and the TST in male CD-1, C57BL/6, DBA and BALB/c mice. We observed strain differences in baseline immobility time, with CD-1 mice showing the longest and DBA mice showing the shortest. In contrast, DBA and BALB/c mice showed the highest sensitivity to FLX, whereas CD-1 and C57BL/6 mice showed the lowest sensitivity. Also we found strain differences in both the total 5-HTT protein level and the membrane-bound 5-HTT level (estimated by V max) as follows: DBA>BALB/c>CD-1=C57BL/6. The uptake efficiency of the membrane-bound 5-HTT (estimated by 1/K m) was highest in DBA and BALB/c mice and lowest in CD-1 and C57BL/6 mice. A correlation analysis of subregions within the hippocampus revealed that immobility time was negatively correlated with V max and positively correlated with K m in the hippocampus. Therefore a higher uptake capacity of the membrane-bound 5-HTT in the hippocampus was associated with lower baseline immobility and greater sensitivity to FLX. These results suggest that alterations in hippocampal 5-HTT activity may contribute to mouse strain differences in the FST and the TST.

Intestinal epithelial cells contribute to Citrobacter rodentium induced infectious colitis through an NF-κB-dependent mechanism (MUC2P.826)

Abstract Exposing mice to a psychological stressor during challenge with the enteric pathogen Citrobacter rodentium (Cr) exacerbates Cr-induced infectious colitis. Enhanced recruitment of inflammatory monocytes to the colon, via a CCL2-dependent mechanism, is essential for the exacerbation of infectious colitis by stressor exposure, however the cell type responsible for the increase of colonic CCL2 is unknown. Previous evidence demonstrates that Cr-induced CCL2 is through an NF-κB mediated mechanism, thus this study was designed to test the hypothesis that NF-κB-derived gene expression from intestinal epithelial cells is necessary for the exacerbation of colitis via the recruitment of inflammatory monocytes, as well as the corollary hypothesis that inflammatory monocytes contribute to infectious colitis also via NF-κB activation. To test these hypotheses, two different strains of mice were challenged with Cr in which classical NF-κB activation is defective via the deletion of IKKβ in either intestinal epithelial cells (IKKβΔIEC) or myeloid-derived cells (IKKβΔMY). There was a reduction in Cr-induced colon mass, colonic histopathology, and colonic inflammatory mediator gene expression in IKKβΔIEC mice as compared to wild type controls. In addition, Cr-induced colon mass, histopathology, and colonic gene expression is further reduced in IKKβΔMY mice. Together, these data illustrate the deleterious effects of pathogen induced NF-κB activation has during enteric pathogen challenge.

Use of humanized mouse models for the study of idiopathic CD4 lymphocytopenia (HUM7P.313)

Abstract Patients with Idiopathic CD4 Lymphocytopenia (ICL) have low circulating CD4 T-cell counts and develop opportunistic diseases and papillomavirus-related dysplasia. The etiology of ICL is unknown but the low numbers of CD4 T-cells could be explained by decreased thymic production, increased cell death, and/or increased migration or retention of the T cells in secondary lymphoid organs or tissues. To distinguish between these three possibilities we set up a humanized mouse model by transferring either peripheral blood mononuclear cells (PBMC), or Hematopoietic Stem Cells (HSC) from ICL patients or healthy controls (HC) into immune-compromised mice. First, we transferred HC cells into three different strains of mice to identify the most efficient and reproducible host for the human cells. We found that NOD-RAGKO-γcKO (NRG) mice represented the best model, as one to four weeks after transferring PBMC into NRG mice, we reproducibly found human T cells in blood, spleen, lymph node and bone marrow with no graft versus host disease. We next transferred PBMC from either HC or ICL patients into NRG mice to compare survival, expansion, phenotype and migration properties of the human cells. Preliminary results show that mice that received ICL cells developed lymphocytopenia comparable to ICL patients. These data encourage further use of this humanized mouse model to identify the etiology and pathogenesis of ICL and perhaps other human immune-deficiencies that affect T-cell homeostasis.

Chlamydial induction of hydrosalpinx in 11 strains of mice reveals multiple host mechanisms for preventing upper genital tract pathology.

The female lower genital tract is constantly exposed to microbial infection, some of which can ascend to and cause pathology such as hydrosalpinx in the upper genital tract, which can affect fertility. To understand host mechanisms for preventing upper genital tract pathology, we screened 11 inbred strains of mice for hydrosalpinx induction by C. muridarum. When examined on days 60 to 80 after intravaginal infection, the 11 strains fell into 3 groups based on their hydrosalpinx severity: CBA/J and SJL/J mice were highly susceptible with a hydrosalpinx score of 5 or greater; Balb/c, C57BL/6J, C57BL/10J, C3H/HeJ and C3H/HeN were susceptible with a score between 1 and <5; NOD/ShiLtJ, DBA/1J, DBA/2J and A/J were resistant with a score of <1. The diverse range of mouse susceptibility to hydrosalpinx induction may reflect the varied clinical outcomes of C. trachomatis-infected women. When the 11 strains were infected via an intrauterine inoculation to bypass the requirement for ascension, higher incidence and more severe hydrosalpinges were induced in most mice, indicating that the interaction between chlamydial ascension and host control of ascension is critical for determining susceptibility to hydrosalpinx development in many mice. However, a few mouse strains resisted significant exacerbation of hydrosalpinx by intrauterine infection, indicating that these mice have evolved ascension-independent mechanisms for preventing upper genital tract pathology. Together, the above observations have demonstrated that different strains of mice can prevent upper genital tract pathology by using different mechanisms.

A comparative study of experimental mouse models of central nervous system demyelination

Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination in different strains of mice. This model differs from most other models in that it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG35–55, MBP35–47, and PLP190–209 models of EAE with our HSV-IL-2-induced MS model. Mice with HSV-IL-2-induced and MOG-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord, and optic nerves. In contrast, no demyelination was detected in the optic nerves of MBP- and PLP-injected mice. IFN-β injections significantly reduced demyelination in brains of all groups, in the spinal cords of the MOG and MBP groups, and completely blocked it in the spinal cords of the PLP and HSV-IL-2 groups as well as in optic nerves of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, while IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS.

The peculiarities of age-related changes in the cellular composition of bone marrow, pineal melatonin-forming function, and thymus endocrine function in mice of different strains

A comparative analysis of the numbers of fibroblast colony-forming (CFC-F) and granulocyte-macrophage colony-forming (CFC-GM) progenitor cells in the bone marrow, as well as the thymulin and melatonin content in the blood of young and old mice of the CBA/Ca and FVB/N strains was carried out. Only a tendency toward an increasing amount of CFC-F and CFC-GM cells in the bone marrow of aging CBA/Ca mice was observed and these indices changed significantly in FVB/N mice. The strain-dependent differences of the age-related changes in the biological properties of the cellular composition of the bone marrow are largely associated with the peculiarities of relationships between the pineal gland and thymus functions in mice of different strains with aging.

Role of Recently Migrated Monocytes in Cigarette Smoke-Induced Lung Inflammation in Different Strain of Mice

SESSION TITLE: Tobacco Cessation and Prevention Posters

On Medawar's ‘Actively acquired tolerance of foreign cells’

The fields of dermatology and transplantation biology have recently come together in clinical trials of bone marrow transplantation for severe inherited blistering skin diseases. But the original link between these two disciplines goes back to an extraordinary publication in 1953 in Nature by Peter Medawar and colleagues that explored the immunological basis of successful skin transplantation between different strains of mice and how 'foreign' antigens could be perceived as 'self'. This work led to the emergence of blood and bone marrow transplantation and thus transformed the practice of modern medicine.

Hindlimb Suspension and SPE-Like Radiation Impairs Clearance of Bacterial Infections

A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health.

Gene expression differences in the duodenum of 129/Sv and DBA/2 mice compared with that of C57BL/6J mice

We compared the cadmium (Cd) concentration in the liver and kidney of different strains of mice after exposure to 50 ppm Cd for 30 days via drinking water. Cd concentration in the liver and kidney of C57BL/6J mice were higher than those of 129/Sv and DBA/2 mice. Since orally ingested heavy metals are absorbed in the small intestine and then widely distributed to target tissues, microarray analyses were performed to compare the expression levels of transport-related genes in the duodenum between C57BL/6J mice and 129/Sv or DBA/2 mice. The expression levels of 9 and 11 genes were elevated more than 2.0-fold and 13 and 12 genes were reduced less than 0.5-fold in 129/Sv mice and DBA/2 mice, respectively. Among these low expressed genes, 10 genes (Slc2a2, Slc5a1, Slc16a2, Slc22a13, Slc22a18, Slc25a11, Slc36a1, Slco6c1, Abca3 and Abcd1) were common between the two types of strains. These results suggest that some of those genes might be involved in Cd absorption and its toxicity.

Comparison of Apolipoprotein E Knockout Mice and Spontaneously Hyperlipidemic Mice in Porphyromonas gingivalis-Induced Atherosclerosis

Porphyromonas gingivalis was shown to accelerate atheroma formation in murine models such as apolipoprotein E knockout (ApoE-KO) mice and BALB/c. apoE-deficient spontaneously hyperlipidemic (C. KOR-Apoeshl) mice. The purpose of this study is to characterize mouse gender and strain differences in P. gingivalis-induced atherosclerosis. Male and female ApoE-KO mice (10 weeks old) and age- and sex-matched C. KOR-Apoeshl mice were intravenously injected with P. gingivalis three times a week for 3 weeks. Mice were then killed at 14 weeks. Atherosclerotic plaques in the proximal aorta were determined by Oil Red O staining. Serum lipid parameters (total cholesterol, TC; high density lipoprotein, HDL; and low density lipoprotein, LDL) and body weights were evaluated. P. gingivalis injection significantly enhanced the formation of atherosclerotic plaque in both ApoE-KO and Apoeshl mice. Moreover, atherosclerotic lesion area was slightly larger in ApoE-KO mice than in Apoeshl mice, while both model mice displayed similar body weight gain regardless of bacterial infection. The weight gain of male was larger than that of female in the period, and the TC of Apoeshl mice was higher than that of ApoE-KO mice. Furthermore, P. gingivalis injection had elevated serum TC and LDL levels compared to the non-injected Apoeshl mice group. These results suggest that P. gingivalis induces atherosclerosis in both ApoE-KO and Apoeshl mice subsequently increasingTC and LDL levels. Thus, the Apoeshl mice may serve as a substitute for ApoEKO mice at the point of it being more natural and superior in examination of temporal change of morbidity, if we take account the import cost and the complication of maintenance of genetically modified mice.

The tryptophan utilization concept in pregnancy.

The decrease in maternal plasma total (free + albumin-bound) tryptophan (Trp) during the third pregnancy trimester is attributed to induction of indoleamine 2,3-dioxygenase (IDO). When measured, free [Trp] is increased because of albumin depletion and non-esterified fatty acid elevation. The Trp depletion concept in pregnancy is therefore not supported because of incorrect interpretation of changes in Trp disposition and also for not addressing mouse strain differences in Trp-related responses and potential inhibition of Trp transport by the IDO inhibitor 1-methyl tryptophan. Application of the Trp utilization concept in pregnancy offers several physiological advantages favoring fetal development and successful outcome, namely provision of Trp for fetal protein synthesis and growth, serotonin for signaling pathways, kynurenic acid for neuroprotection, quinolinic acid for NAD+ synthesis, and other kynurenines for suppression of T cell responses. An excessive increase in Trp availability could compromise pregnancy by undermining T cell suppression, e.g., in pre-eclampsia.

Generation of a New Congenic Mouse Strain with Enhanced Chymase Expression in Mast Cells

Mast cells are effector cells best known for their roles in IgE-associated allergy, but they also play a protective role in defense against pathogens. These cells express high levels of proteases including chymase, tryptase and carboxypeptidase. In the present study, we identified a congenic strain of C57BL/6 mice expressing an extraordinarily high level of chymases Mcp-2 and Mcp-4 in mast cells. The overexpression was associated with variant Mcp-2 and Mcp-4 genes originated from DBA/2 mice that also expressed high levels of the two enzymes. Real time PCR analysis revealed that Mcp-2 and Mcp-4 were selectively overexpressed as tryptases, Cpa3 and several other chymases were kept at normal levels. Reporter gene assays demonstrated that single-nucleotide polymorphisms (SNPs) in the promoter region of Mcp-2 gene may be partly responsible for the increased gene transcription. Our study provides a new model system to study the function of mast cell chymases. The data also suggest that expression of chymases differs considerably in different strains of mice and the increased chymase activity may be responsible for some unique phenotypes observed in DBA/2 mice.

Modulation of Strain-Specific Differences in Gene Expression by Cannabinoid Type 2 Receptor Deficiency

Previous studies have shown that the skeletal consequences of cannabinoid receptor deficiency differ in different strains of mice. In order to explore the mechanisms responsible, we analysed global gene expression in bone from wild-type CD1 mice and littermates with targeted inactivation of the type 2 cannabinoid receptor (Cnr2 (-/-)) and compared the results with those obtained from a similar analysis of wild-type and Cnr2 (-/-) C57BL/6 mice. Trabecular bone volume was increased in Cnr2 (-/-) CD1 mice compared with wild-type littermates but decreased in Cnr2 (-/-) C57BL/6 mice. Microarray analysis identified 354 genes in which substantial differences in gene expression (>1.5-fold) were observed that were specifically affected by Cnr2 deficiency. Bioinformatic analysis of data from wild-type mice of each strain revealed Cnr2-dependent differences in expression of genes clustering within the gene ontology (GO) terms immune response (p < 0.0001), positive regulation of response to stimulus (p < 0.0001), nucleotide binding (p = 0.002), and ribonucleotide binding (p = 0.003). Bioinformatic analysis of data from Cnr2 (-/-) mice of each strain revealed associations between GO terms corresponding to the extracellular region (p = 0.002), the cell surface (p = 0.02), antigen binding (p = 0.03), external side of plasma membrane (p = 0.04), and regulation of the force of heart contraction (p = 0.04). We conclude that Cnr2 deficiency affects expression of a large number of genes in different strains of mice, and that these differences are likely to be responsible in part for the differences in skeletal phenotype that we and others have observed in mice with defective cannabinoid receptor signalling in different genetic backgrounds.

Reduced Live Organism Recovery and Lack of Hydrosalpinx in Mice Infected with Plasmid-Free Chlamydia muridarum

Plasmid-free Chlamydia trachomatis and Chlamydia muridarum fail to induce severe pathology. To evaluate whether the attenuated pathogenicity is due to insufficient infection or inability of the plasmidless chlamydial organisms to trigger pathological responses, we compared plasmid-competent and plasmid-free C. muridarum infections in 5 different strains of mice. All 5 strains developed hydrosalpinx following intravaginal inoculation with plasmid-competent, but not inoculation with plasmid-free, C. muridarum. The lack of hydrosalpinx induction by plasmid-free C. muridarum correlated with significantly reduced live organism recovery from the lower genital tract and shortened infection in the upper genital tract. The plasmid-free C. muridarum organisms failed to induce hydrosalpinx even when the organisms were directly inoculated into the oviduct via an intrabursal injection, which was accompanied by significantly reduced survival of the plasmidless organisms in the genital tracts. Furthermore, plasmid-competent C. muridarum organisms after UV inactivation were no longer able to induce hydrosalpinx even when directly delivered into the oviduct at a high dose. Together, these observations suggest that decreased survival of and shortened infection with plasmid-free C. muridarum may contribute significantly to its attenuated pathogenicity. We conclude that adequate live chlamydial infection in the oviduct may be necessary to induce hydrosalpinx.

Mouse strain differences in metabolic fluxes and function of ex vivo working hearts

In mice, genetic background is known to influence various parameters, including cardiac function. Its impact on cardiac energy substrate metabolism-a factor known to be closely related to function and contributes to disease development-is, however, unclear. This was examined in this study. In commonly used control mouse substrains SJL/JCrNTac, 129S6/SvEvTac, C57Bl/6J, and C57Bl/6NCrl, we assessed the functional and metabolic phenotypes of 3-mo-old working mouse hearts perfused ex vivo with physiological concentrations of (13)C-labeled carbohydrates (CHO) and a fatty acid (FA). Marked variations in various functional and metabolic flux parameters were observed among all mouse substrains, although the pattern observed differed for these parameters. For example, among all strains, C57Bl/6NCrl hearts had a greater cardiac output (+1.7-fold vs. SJL/JCrNTac and C57Bl/6J; P < 0.05), whereas at the metabolic level, 129S6/SvEvTac hearts stood out by displaying (vs. all 3 strains) a striking shift from exogenous FA (~-3.5-fold) to CHO oxidation as well as increased glycolysis (+1.7-fold) and FA incorporation into triglycerides (+2-fold). Correlation analyses revealed, however, specific linkages between 1) glycolysis, FA oxidation, and pyruvate metabolism and 2) cardiac work, oxygen consumption with heart rate, respectively. This implies that any genetically determined factors affecting a given metabolic flux parameter may impact on the associated functional parameters. Our results emphasize the importance of selecting the appropriate control strain for cardiac metabolic studies using transgenic mice, a factor that has often been neglected. Understanding the molecular mechanisms underlying the diversity of strain-specific cardiac metabolic and functional profiles, particularly the 129S6/SvEvTac, may ultimately disclose new specific metabolic targets for interventions in heart disease.

Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis

Ethnopharmacological relevancePomegranate (Punica granatum L.; Lythraceae) has traditionally been used for the treatment of various inflammatory diseases, including ulcerative colitis (UC). Because its fruits and extracts are rich in ellagitannins, which release ellagic acid when hydrolyzed, consumption of pomegranate products is currently being widely promoted for their potential health effects, including the prevention of inflammatory diseases and cancer. To evaluate the anti-inflammatory effects of ellagic acid on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in two different strains of mice and to elucidate its possible mechanisms of action. Materials and methodsIn the acute UC model, female Balb/C mice were treated with DSS (5%) for seven days while concomitantly receiving a dietary supplement of ellagic acid (2%). In the chronic UC model, female C57BL/6 mice received four week-long cycles of DSS (1% and 2%) interspersed with week-long recovery periods along with a diet supplemented with ellagic acid (0.5%). ResultsIn acute model of UC, ellagic acid ameliorated disease severity slightly as observed both macroscopically and through the profile of inflammatory mediators (IL-6, TNF-α, and IFN-γ). In the chronic UC model, ellagic acid significantly inhibited the progression of the disease, reducing intestinal inflammation and decreasing histological scores. Moreover, mediators such as COX-2 and iNOS were downregulated and the signaling pathways p38 MAPK, NF-κB, and STAT3 were blocked. ConclusionsOur study reinforces the hypothetical use of ellagic acid as an anti-inflammatory complement to conventional UC treatment in chronic UC patients and could be considered in the dietary prevention of intestinal inflammation and related cancer development.

The role of mouse strain differences in the susceptibility to fibrosis: a systematic review.

In humans, a number of genetic factors have been linked to the development of fibrosis in a variety of different organs. Seeking a wider understanding of this observation in man is ethically important. There is mounting evidence suggesting that inbred mouse strains with different genetic backgrounds demonstrate variable susceptibility to a fibrotic injury. We performed a systematic review of the literature describing strain and organ specific response to injury in order to determine whether genetic susceptibility plays a role in fibrogenesis. Data were collected from studies that were deemed eligible for analysis based on set inclusion criteria, and findings were assessed in relation to strain of mouse, type of injury and organ of investigation. A total of 44 studies were included covering 21 mouse strains and focusing on fibrosis in the lung, liver, kidney, intestine and heart. There is evidence that mouse strain differences influence susceptibility to fibrosis and this appears to be organ specific. For instance, C57BL/6J mice are resistant to hepatic, renal and cardiac fibrosis but susceptible to pulmonary and intestinal fibrosis. However, BALB/c mice are resistant to pulmonary fibrosis but susceptible to hepatic fibrosis. Few studies have assessed the effect of the same injury stimulus in different organ systems using the same strains of mouse. Such mouse strain studies may prove useful in elucidating the genetic as well as epigenetic factors in humans that could help determine why some people are more susceptible to the development of certain organ specific fibrosis than others.