The landscape of PBMC methylome in canine mammary tumors reveals the epigenetic regulation of immune marker genes and its potential application in predicting tumor malignancy.

BACKGROUND: Genome-wide dysregulation of CpG methylation accompanies tumor progression and characteristic states of cancer cells, prompting a rationale for biomarker development. Understanding how the archetypic epigenetic modification determines systemic contributions of immune cell types is the key to further clinical benefits. RESULTS: In this study, we characterized the differential DNA methylome landscapes of peripheral blood mononuclear cells (PBMCs) from 76 canines using methylated CpG-binding domain sequencing (MBD-seq). Through gene set enrichment analysis, we discovered that genes involved in the growth and differentiation of T- and B-cells are highly methylated in tumor PBMCs. We also revealed the increased methylation at single CpG resolution and reversed expression in representative marker genes regulating immune cell proliferation (BACH2, SH2D1A, TXK, UHRF1). Furthermore, we utilized the PBMC methylome to effectively differentiate between benign and malignant tumors and the presence of mammary gland tumors through a machine-learning approach. CONCLUSIONS: This research contributes to a better knowledge of the comprehensive epigenetic regulation of circulating immune cells responding to tumors and suggests a new framework for identifying benign and malignant cancers using genome-wide methylome.

ABCA9, an ER cholesterol transporter, inhibits breast cancer cell proliferation via SREBP-2 signaling.

The association between cholesterol metabolism and cancer development and progression has been recently highlighted. However, the role and function of many cholesterol transporters remain largely unknown. Here, we focused on the ATP-binding cassette subfamily A member 9 (ABCA9) transporter given that its expression is significantly downregulated in both canine mammary tumors and human breast cancers, which in breast cancer patients correlates with poor prognosis. We found that ABCA9 is mainly present in the endoplasmic reticulum (ER) and is responsible for promoting cholesterol accumulation in this structure. Accordingly, ABCA9 inhibited sterol-regulatory element binding protein-2 (SREBP-2) translocation from the ER to the nucleus, a crucial step for cholesterol synthesis, resulting in the downregulation of cholesterol synthesis gene expression. ABCA9 expression in breast cancer cells attenuated cell proliferation and reduced their colony-forming abilities. We identified ABCA9 expression to be regulated by Forkhead box O1 (FOXO1). Inhibition of PI3K induced enhanced ABCA9 expression through the activation of the PI3K-Akt-FOXO1 pathway in breast cancer cells. Altogether, our study suggests that ABCA9 functions as an ER cholesterol transporter that suppresses cholesterol synthesis via the inhibition of SREBP-2 signaling and that its restoration halts breast cancer cell proliferation. Our findings provide novel insight into the vital role of ABCA9 in breast cancer progression.

Effects of air blower and pump failures on the performance of A2O processes for wastewater treatment.

The unexpected failure of equipment such as pumps and fans in wastewater treatment plants can reduce wastewater treatment efficiency, leading to direct leakage of untreated wastewater into the environment. It is hence important to predict the possible consequences of equipment failure to minimize the leakage of harmful substances. This study examines the impacts of equipment shutdown on the performance and recovery time of a laboratory-scale anaerobic/anoxic/aerobic system with regard to reactor conditions and water quality. Two days after the air blowers are stopped, the concentrations of the soluble chemical oxygen demand, NH4-N, and PO4-P in the effluent of the settling tank increase to 122 mg/L, 23.8 mg/L, and 46.6 mg/L, respectively. These concentrations return to their initial values after 12, 24, and 48 h of restarting the air blowers. The concentrations of PO4-P and NO3-N in the effluent increase to 58 mg/L and 20 mg/L, respectively, about 24 h after stopping the return activated sludge and mixed liquor recirculation pumps, owing to the release of phosphates in the settling tank and inhibition of denitrification.

Clinical characteristics and long-term outcome of 223 patients with mycosis fungoides at a single tertiary center in Korea: A 29-year review.

BACKGROUND: Data regarding Asian patients with mycosis fungoides (MF) are limited. OBJECTIVE: We aimed to investigate the clinical profile and long-term outcomes of patients with MF in Korea. METHODS: A retrospective review of 223 patients with MF who were followed up for more than 6 months or died of MF within 6 months of diagnosis was performed. RESULTS: Approximately 96.4% and 3.6% of the patients had an early stage and advanced stage, respectively. The mean age at diagnosis was 44.8 years. The mean duration of symptoms before diagnosis was 47.0 months. Various subtypes were noted, including mycosis fungoides palmaris et plantaris (21.5%), folliculotropic (8.5%), pityriasis lichenoides-like (6.7%), ichthyosiform (4.0%), lichenoid purpura-like (2.7%), and hypopigmented (2.2%) MF. Juvenile patients accounted for 16.6%. The higher the skin T stage, the poorer the response to treatment. The 10-year overall survival was 96.8% in early-stage patients and 25.0% in advanced-stage patients. General prognosis was favorable, while recurrence and subtype switching were seen in 29.4% and 2.7% of patients, respectively. LIMITATIONS: Our patients may not represent all Korean patients with MF. CONCLUSION: MF in Korea has a high proportion of variants, a younger age at onset, and favorable prognosis. A high index of suspicion and skin biopsy are needed for early diagnosis.

Impact of Acetate in Reduction of Perchlorate by Mixed Microbial Culture under the Influence of Nitrate and Sulfate.

The biological reduction of slow degradation contaminants such as perchlorate (ClO4-) is considered to be a promising water treatment technology. The process is based on the ability of a specific mixed microbial culture to use perchlorate as an electron acceptor in the absence of oxygen. In this study, batch experiments were conducted to investigate the effect of nitrate on perchlorate reduction, the kinetic parameters of the Monod equation and the optimal ratio of acetate to perchlorate for the perchlorate reducing bacterial consortium. The results of this study suggest that acclimated microbial cultures can be applied to treat wastewater containing high concentrations of perchlorate. Reactor experiments were carried out with different hydraulic retention times (HRTs) to determine the optimal operating conditions. A fixed optimal HRT and the effect of nitrate on perchlorate reduction were investigated with various concentrations of the electron donor. The results showed that perchlorate reduction occurred after nitrate removal. Moreover, the presence of sulfate in wastewater had no effect on the perchlorate reduction. However, it had little effect on biomass concentration in the presence of nitrate during exposure to a mixed microbial culture, considering the nitrate as the inhibitor of perchlorate reduction by reducing the degradation rate. The batch scale experiment results illustrated that for efficient operation of perchlorate reduction, the optimal acetate to perchlorate ratio of 1.4:1.0 would be enough. Moreover, these experiments found the following results: the kinetic parameters equivalent to Y = 0.281 mg biomass/mg perchlorate, Ks = 37.619 mg/L and qmax = 0.042 mg perchlorate/mg biomass/h. In addition, anoxic-aerobic experimental reactor results verify the optimal HRT of 6 h for continuous application. Furthermore, it also illustrated that using 600 mg/L of acetate as a carbon source is responsible for 100% of nitrate reduction with less than 50% of the perchlorate reduction, whereas at 1000 mg/L acetate, approximately 100% reduction was recorded.

Use of ballasted flocculation (BF) sludge for the manufacturing of lightweight aggregates.

Ballasted flocculation (BF) is an efficient way to remove the turbidity from surface water. The objective of the present study is to optimize the ballast (magnetite), coagulant (poly aluminum chloride) concentration and pH for efficient turbidity removal from surface water. To do this, the sludge produced from an optimized dose of a BF treatment was utilized for the production of lightweight (LW) aggregates by combining it with hard clay and sewage sludge. The LW aggregates were formed by means of rapid sintering in the temperature range of 1000-1200 °C with an exposure time of 10 min. The physical properties of the LW aggregates, in this case the leaching of heavy metals, the bulk density and the microstructure, were investigated. The results indicated that corresponding ballast and coagulant concentrations of 0.75 g/L and 30 mg/L (poly aluminum chloride (PAC)) resulted in the maximum removal efficiency of ≈95%. Using a mixture of BF sludge (30 wt%), dry sewage sludge (20 wt%), and hard clay (50 wt%), aggregates with a density of around 1.0 g/cm3 could be produced. In addition, it was confirmed that the manufactured aggregate was environmentally stable as the elution of heavy metals was suppressed.

Coagulation Behavior of Antimony Oxyanions in Water: Influence of pH, Inorganic and Organic Matter on the Physicochemical Characteristics of Iron Precipitates.

The presence of inorganic and organic substances may alter the physicochemical properties of iron (Fe) salt precipitates, thereby stabilizing the antimony (Sb) oxyanions in potable water during the chemical treatment process. Therefore, the present study aimed to examine the surface characteristics, size of Fe flocs and coagulation performance of Sb oxyanions under different aqueous matrices. The results showed that surface properties of Fe flocs significantly varies with pH in both Sb(III, V) suspensions, thereby increasing the mobility of Sb(V) ions in alkaline conditions. The negligible change in surface characteristics of Fe flocs was observed in pure water and Sb(III, V) suspension at pH 7. The key role of Van der Waals forces of attraction as well as hydration force in the aggregation of early formed flocs were found, with greater agglomeration capability at higher more ferric chloride dosage. The higher Sb(V) loading decreased the size of Fe flocs and reversed the surface charge of precipitates, resulting in a significant reduction in Sb(V) removal efficiency. The competitive inhibition effect on Sb(III, V) removal was noticed in the presence of phosphate anions, owing to lowering of ζ-potential values towards more negative trajectory. The presence of hydrophobic organic matter (humic acid) significantly altered the surface characteristics of Fe flocs, thereby affecting the coagulation behavior of Sb in water as compared to the hydrophilic (salicylic acid). Overall, the findings of this research may provide a new insight into the variation in physicochemical characteristics of Fe flocs and Sb removal behavior in the presence of inorganic and organic compounds during the drinking water treatment process.

CXCL5 secreted from macrophages during cold exposure mediates white adipose tissue browning.

Adipose tissue affects metabolic-related diseases because it consists of various cell types involved in fat metabolism and adipokine release. CXC ligand 5 (CXCL5) is a member of the CXC chemokine family and is highly expressed by macrophages in white adipose tissue (WAT). In this study, we generated and investigated the function of CXCL5 in knockout (KO) mice using CRISPR/Cas9. The male KO mice did not show significant phenotype differences in normal conditions. However, proteomic analysis revealed that many proteins involved in fatty acid beta-oxidation and mitochondrial localization were enriched in the inguinal WAT (iWAT) of Cxcl5 KO mice. Cxcl5 KO mice also showed decreased protein and transcript expression of genes associated with thermogenesis, including uncoupling protein 1 (UCP1), a well-known thermogenic gene, and increased expression of genes associated with inflammation. The increase in UCP1 expression in cold conditions was significantly retarded in Cxcl5 KO mice. Finally, we found that CXCL5 treatment increased the expression of transcription factors that mediate Ucp1 expression and Ucp1 itself. Collectively, our data show that Ucp1 expression is induced in adipocytes by CXCL5, which is secreted upon ß-adrenergic stimulation by cold stimulation in M1 macrophages. Our data indicate that CXCL5 plays a crucial role in regulating energy metabolism, particularly upon cold exposure. These results strongly suggest that targeting CXCL5 could be a potential therapeutic strategy for people suffering from disorders affecting energy metabolism.

Spatiotemporal expression of long noncoding RNA Moshe modulates heart cell lineage commitment.

The roles of long non-coding RNA (LncRNA) have been highlighted in various development processes including congenital heart defects (CHD). Here, we characterized the molecular function of LncRNA, Moshe (1010001N08ik-203), one of the Gata6 antisense transcripts located upstream of Gata6, which is involved in both heart development and the most common type of congenital heart defect, atrial septal defect (ASD). During mouse embryonic development, Moshe was first detected during the cardiac mesoderm stage (E8.5 to E9.5) where Gata6 is expressed and continues to increase at the atrioventricular septum (E12.5), which is involved in ASD. Functionally, the knock-down of Moshe during cardiogenesis caused significant repression of Nkx2.5 in cardiac progenitor stages and resulted in the increase in major SHF lineage genes, such as cardiac transcriptional factors (Isl1, Hand2, Tbx2), endothelial-specific genes (Cd31, Flk1, Tie1, vWF), a smooth muscle actin (a-Sma) and sinoatrial node-specific genes (Shox2, Tbx18). Chromatin Isolation by RNA Purification showed Moshe activates Nkx2.5 gene expression via direct binding to its promoter region. Of note, Moshe was conserved across species, including human, pig and mouse. Altogether, this study suggests that Moshe is a heart-enriched lncRNA that controls a sophisticated network of cardiogenesis by repressing genes in SHF via Nkx2.5 during cardiac development and may play an important role in ASD.

METTL8 mRNA Methyltransferase Enhances Cancer Cell Migration via Direct Binding to ARID1A.

The association of RNA modification in cancer has recently been highlighted. Methyltransferase like 8 (METTL8) is an enzyme and its role in mRNA m3C modification has barely been studied. In this study, we found that METTL8 expression was significantly up-regulated in canine mammary tumor and investigated its functional roles in the tumor process, including cancer cell proliferation and migration. METTL8 expression was up-regulated in most human breast cancer cell lines tested and decreased by Yin Yang 1 (YY1) transcription factor knockdown, suggesting that YY1 is a regulating transcription factor. The knockdown of METTL8 attenuated tumor cell growth and strongly blocked tumor cell migration. AT-rich interactive domain-containing protein 1A (ARID1A) was identified as a candidate mRNA by METTL8. ARID1A mRNA binds to METTL8 protein. ARID1A mRNA expression was not changed by METTL8 knockdown, but ARID1A protein level was significantly increased. Collectively, our study indicates that METTL8 up-regulated by YY1 in breast cancer plays an important role in cancer cell migration through the mRNA modification of ARID1A, resulting in the attenuation of its translation.

Removal of Tannic Acid Stabilizes CuO Nanoparticles from Aqueous Media by PAFC: Effect of Process Conditions and Water Chemistry.

The increased utilization of CuO nanoparticles (CuO NPs) in various fields has raised concerns about their discharge into water containing a wide range of organic ligands. Moreover, the adsorption of these ligands can stabilize the CuO NPs in drinking water treatment plants. Thus, their removal from potable water is important to mitigate the risk to humans. The present study explored the efficacy of the coagulation-sedimentation (C/S) process for the removal of tannic acid (TA)-stabilized CuO NPs using polyaluminum ferric chloride (PAFC) as a coagulant. Moreover, the influence of process conditions (stirring speed) and water chemistry (i.e., pH and ionic strength (IS)) were also investigated to determine their impact on removal. The results showed that stirring speed in the reaction phase significantly affected the removal due to increased flocculation compared with stirring speed in the mixing phase. In addition, pH and IS affect the colloidal stability and removal efficiency of CuO NPs. A relatively better removal performance (<99%) of CuO NPs was found at lower coagulant dosage in the pH range 6-8. The addition of organic ligands reversed the surface charge potential and enhanced the colloidal stability of CuO NPs, resulting in the destabilization of TA-CuO NPs, thereby reducing the optimum PAFC dosage for removal. By contrast, the IS above the critical coagulation concentration decreased the removal efficiency due to inhibition of the ionic activity of PAFC hydrolysate in the aqueous environment. Fourier transform infrared findings of TA-CuO NPs composite flocs suggest that the primary removal mechanism might be mediated via the combined effect of neutralization, complexation as well as adsorption.

Adsorption Capacities of Iron Hydroxide for Arsenate and Arsenite Removal from Water by Chemical Coagulation: Kinetics, Thermodynamics and Equilibrium Studies.

Arsenic (As)-laden wastewater may pose a threat to biodiversity when released into soil and water bodies without treatment. The current study investigated the sorption properties of both As(III, V) oxyanions onto iron hydroxide (FHO) by chemical coagulation. The potential mechanisms were identified using the adsorption models, ζ-potential, X-ray diffraction (XRD) and Fourier Transform Infrared Spectrometry (FT-IR) analysis. The results indicate that the sorption kinetics of pentavalent and trivalent As species closely followed the pseudo-second-order model, and the adsorption rates of both toxicants were remarkably governed by pH as well as the quantity of FHO in suspension. Notably, the FHO formation was directly related to the amount of ferric chloride (FC) coagulant added in the solution. The sorption isotherm results show a better maximum sorption capacity for pentavalent As ions than trivalent species, with the same amount of FHO in the suspensions. The thermodynamic study suggests that the sorption process was spontaneously exothermic with increased randomness. The ζ-potential, FT-IR and XRD analyses confirm that a strong Fe-O bond with As(V) and the closeness of the surface potential of the bonded complex to the point of zero charge (pHzpc) resulted in the higher adsorption affinity of pentavalent As species than trivalent ions in most aquatic conditions. Moreover, the presence of sulfates, phosphates, and humic and salicylic acid significantly affected the As(III, V) sorption performance by altering the surface properties of Fe precipitates. The combined effect of charge neutralization, complexation, oxidation and multilayer chemisorption was identified as a major removal mechanism. These findings may provide some understanding regarding the fate, transport and adsorption properties onto FHO of As oxyanions in a complex water environment.

Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases.

Cholesterol is an essential cell component that functions to create and maintain all kinds of cell membranes and lipoprotein particles. It is crucial to maintain the proper amount of cholesterol at both the cellular and systemic level. Recently, the importance of cholesterol has been reported not only in various cell development processes but also in the development of diseases. Furthermore, the involvement of long non-coding RNAs (lncRNAs), which are regarded as important epigenetic regulators in gene expression, has also been reported in cholesterol homeostasis. It is thus necessary to summarize the research on lncRNAs related to cholesterol with increased interest. This review organized the role of lncRNAs according to the major issues in cholesterol homeostasis: efflux, metabolism and synthesis, and disease process.

ANK2 Hypermethylation in Canine Mammary Tumors and Human Breast Cancer.

Canine mammary tumors (CMT) constitute the most common tumor types found in female dogs. Understanding this cancer through extensive research is important not only for clinical veterinary applications, but also in the scope of comparative oncology. The use of DNA methylation as a biomarker has been noted for numerous cancers in the form of both tissue and liquid biopsies, yet the study of methylation in CMT has been limited. By analyzing our canine methyl-binding domain sequencing (MBD-seq) data, we identified intron regions of canine ANK2 and EPAS1 as differentially methylated regions (DMGs) in CMT. Subsequently, we established quantitative methylation specific PCR (qMSP) of ANK2 and EPAS1 to validate the target hypermethylation in CMT tissue, as well as cell free DNA (cfDNA) from CMT plasma. Both ANK2 and EPAS1 were hypermethylated in CMT and highlighted as potential tissue biomarkers in CMT. ANK2 additionally showed significant hypermethylation in the plasma cfDNA of CMT, indicating that it could be a potential liquid biopsy biomarker as well. A similar trend towards hypermethylation was indicated in HBC at a specific CpG of the ANK2 target on the orthologous human region, which validates the comparative approach using aberrant methylation in CMT.

Transposable element-mediated structural variation analysis in dog breeds using whole-genome sequencing.

Naturally occurring diseases in dogs provide an important animal model for studying human disease including cancer, heart disease, and autoimmune disorders. Transposable elements (TEs) make up ~ 31% of the dog (Canis lupus familiaris) genome and are one of main drivers to cause genomic variations and alter gene expression patterns of the host genes, which could result in genetic diseases. To detect structural variations (SVs), we conducted whole-genome sequencing of three different breeds, including Maltese, Poodle, and Yorkshire Terrier. Genomic SVs were detected and visualized using BreakDancer program. We identified a total of 2328 deletion SV events in the three breeds compared with the dog reference genome of Boxer. The majority of the genetic variants were found to be TE insertion polymorphism (1229) and the others were TE-mediated deletion (489), non-TE-mediated deletion (542), simple repeat-mediated deletion (32), and other indel (36). Among the TE insertion polymorphism, 286 elements were full-length LINE-1s (L1s). In addition, the 49 SV candidates located in the genic regions were experimentally verified and their polymorphic rates within each breed were examined using PCR assay. Polymorphism analysis of the genomic variants revealed that some of the variants exist polymorphic in the three dog breeds, suggesting that their SV events recently occurred in the dog genome. The findings suggest that TEs have contributed to the genomic variations among the three dog breeds of Maltese, Poodle, and Yorkshire Terrier. In addition, the polymorphic events between the dog breeds indicate that TEs were recently retrotransposed in the dog genome.

Concise approach for screening long non-coding RNAs functionally linked to human breast cancer associated genes.

Cancer research studies using next-generation sequencing have revealed a number of genes of which aberrant expression is associated with various cancers. Recently, long non-coding RNA (lncRNA) has been highlighted due to its tissue-specific expression and cell cancerization functions, such as the regulation of key tumor suppressors. In this study, we suggest a very efficient approach to survey lncRNAs putatively associated with breast cancer. We targeted lncRNAs linked with breast cancer associated genes (BCAGs) and analyzed their expression pattern in human breast cancer cell lines. A total of 337 BCAGs were retrieved from literature review and the existence of 121 lncRNAs were identified from the 15 kb up- and downstream regions of the list of genes. Twenty lncRNAs' expression were detectable in human breast cancer cell lines with different expression patterns. Interestingly, the expression of three lncRNAs, two up-regulated (RAD51C v.4, LOC105371849) and one down-regulated (LOC102724064), were closely correlated with adjacent BCAGs (RAD51C, HEATR6 and BRMS1) in breast cancer cell lines. We thus demonstrated association between the lncRNA and its adjacent BCAG using LOC105371849-HEATR6, of which the function and regulation in breast cancer are still unknown. Knockdown of LOC105371849 by siRNA decreased the expression of HEATR6 mRNA in the MCF7 human breast cancer cell line. In conclusion, this study provides a better understanding about the biological roles of lncRNAs in breast cancer and may be useful in the investigation of proper targets for diagnostic and/or therapeutic breast cancer markers using public databases.

The Role of Nitrosamine (NNK) in Breast Cancer Carcinogenesis.

Smoking cigarettes is one of the most concerning issues that leads to tobacco-related cancers and can even result in death. Therefore, these issues should be addressed with a great sense of urgency with low-cost and simple approaches. Over the past several years, the scientific community has attempted to find solutions to overcome this issue. Thus, a large number of excellent studies have been reported in this field, and summarizing these results and providing important roadmaps for future studies is currently of great importance. Finding an outstanding solution to address aforementioned issue would be of great value to the community and to the social. Tobacco contains thousands of chemicals, and sixty-nine compounds have been established as human carcinogens; specifically, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the strongest carcinogen among the tobacco-specific nitrosamines. Tobacco carcinogens are also linked to mammary gland pathogenesis and increased risk of developing many cancers, including breast cancer, the most common cancer in women worldwide. This mini-review summarizes the role of NNK and the mechanisms of its receptor, nicotine acetylcholine receptor (nAChR), signaling in breast cancer based on publications identified using the keywords "secondhand smoke (SHS)", "Nitrosamines" and "breast cancer". Furthermore, this review considers the risk of NNK to the public in an effort to reduce exposure to SHS in women and their chances of developing breast cancer.

Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication.

BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) with triple therapy which was considered as standard first-line treatment has decreased to 70-85%. The aim of this study is to compare 7-day triple therapy versus 10-day sequential therapy as the first line treatment. METHODS: Data of 1240 H. pylori positive patients treated with triple therapy or sequential therapy from January 2013 to December 2015 were analyzed retrospectively. The patients who had undertaken previous H. pylori eradication therapy or gastric surgery were excluded. RESULTS: There were 872 (74.3%) patients in the triple therapy group, and 302 (25.7%) patients in the sequential therapy group. There was no significant difference between the two groups regarding age, residence, comorbidities or drug compliance, but several differences were noted in endoscopic characteristics and indication for the treatment. The eradication rate of H. pylori by intention to treat analysis was 64.3% in the triple therapy group, and 81.9% in the sequential therapy group (P = 0.001). In per protocol analysis, H. pylori eradication rate in the triple therapy and sequential therapy group was 81.9 and 90.3%, respectively (P = 0.002). There was no significant difference in overall adverse events between the two groups (P = 0.706). For the rescue therapy, bismuth-containing quadruple therapy showed comparable treatment efficacy after sequential therapy, as following triple therapy. CONCLUSIONS: The eradication rate of triple therapy was below the recommended threshold. Sequential therapy could be effective and tolerable candidate for the first-line H. pylori eradication therapy.

Genomic landscapes of endogenous retroviruses unveil intricate genetics of conventional and genetically-engineered laboratory mouse strains.

Laboratory strains of mice, both conventional and genetically engineered, have been introduced as critical components of a broad range of studies investigating normal and disease biology. Currently, the genetic identity of laboratory mice is primarily confirmed by surveying polymorphisms in selected sets of "conventional" genes and/or microsatellites in the absence of a single completely sequenced mouse genome. First, we examined variations in the genomic landscapes of transposable repetitive elements, named the TREome, in conventional and genetically engineered mouse strains using murine leukemia virus-type endogenous retroviruses (MLV-ERVs) as a probe. A survey of the genomes from 56 conventional strains revealed strain-specific TREome landscapes, and certain families (e.g., C57BL) of strains were discernible with defined patterns. Interestingly, the TREome landscapes of C3H/HeJ (toll-like receptor-4 [TLR4] mutant) inbred mice were different from its control C3H/HeOuJ (TLR4 wild-type) strain. In addition, a CD14 knock-out strain had a distinct TREome landscape compared to its control/backcross C57BL/6J strain. Second, an examination of superantigen (SAg, a "TREome gene") coding sequences of mouse mammary tumor virus-type ERVs in the genomes of the 46 conventional strains revealed a high diversity, suggesting a potential role of SAgs in strain-specific immune phenotypes. The findings from this study indicate that unexplored and intricate genomic variations exist in laboratory mouse strains, both conventional and genetically engineered. The TREome-based high-resolution genetics surveillance system for laboratory mice would contribute to efficient study design with quality control and accurate data interpretation. This genetics system can be easily adapted to other species ranging from plants to humans.