MRLxSM eQTL in Liver by RMA on Ensembl transcripts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE25322 | GEO | 2011/11/28
SECONDARY ACCESSION(S): PRJNA134845
REPOSITORIES: GEO
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Project description:A QTL analysis between inbred mouse strains MRL/MpJ and SM/J was performed to identify genetic loci influencing high-density lipoprotein (HDL) cholesterol and triglycerides (TG) at eight weeks of age in F2 mice fed a chow diet. In order to narrow down lists of candidate genes, expression levels from liver tissue were used to test for differential expression among parental and F1 strains and to scan for eQTL in F2 animals. We provide evidence for Mppe1 (Chr 18) as an HDL QTL candidate gene and Cyp2d26 (Chr 15) as a TG QTL candidate gene. MRL/MpJ (MRL) mice were crossed with male SM/J (SM) mice; their progeny were intercrossed to produce 371 F2 animals. Of these, 282 F2 males and females were profiled with Affy Mouse Gene 1.0 ST arrays for an eQTL study. Three animals from each parental and the F1 strains from each sex, i.e. 18 in total, were also profiled for testing differential expression. A total of 300 samples are included in the dataset. The mice were weaned at 3 weeks on a chow diet. At 13 weeks of age, mice were single housed for 3 days and fasted for 4 hours prior to being sacrificed. Tissue collection was performed between noon and 1pm to avoid variations due to circadian rhythm.
2011-11-28 | E-GEOD-25322 | biostudies-arrayexpress
Project description:Identifying the genes underlying quantitative trait loci (QTL) for disease has proven difficult, mainly due to the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals and test candidate genes. In addition to identifying the causative genes, defining the pathways that are affected by these QTL is of major importance as it can give us insight into the disease process and provide evidence to support candidate genes. In this study we mapped three significant and one suggestive QTL on Chromosomes (Chrs) 1, 4, 15, and 17, respectively, for increased albumin excretion (measured as albumin-to-creatinine ratio) in a cross between the MRL/MpJ and SM/J mouse inbred strains. By combining data from several sources and by utilizing gene expression data, we identified Tlr12 as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL. Among these were the glycan degradation, leukocyte migration, and antigen presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL, but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease. Female MRL/MpJ (MRL) mice were crossed with male SM/J (SM) mice; their progeny were intercrossed to produce 371 F2 animals. Only 173 F2 males were used for this study. This submission represents the expression profiling component of the study.
2011-02-01 | E-GEOD-23310 | biostudies-arrayexpress
Project description:Identifying the genes underlying quantitative trait loci (QTL) for disease has proven difficult, mainly due to the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals and test candidate genes. In addition to identifying the causative genes, defining the pathways that are affected by these QTL is of major importance as it can give us insight into the disease process and provide evidence to support candidate genes. In this study we mapped three significant and one suggestive QTL on Chromosomes (Chrs) 1, 4, 15, and 17, respectively, for increased albumin excretion (measured as albumin-to-creatinine ratio) in a cross between the MRL/MpJ and SM/J mouse inbred strains. By combining data from several sources and by utilizing gene expression data, we identified Tlr12 as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL. Among these were the glycan degradation, leukocyte migration, and antigen presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL, but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease.
2011-02-01 | GSE23310 | GEO
Project description:MRL mice display unusual healing properties. When MRL ear pinnae are hole punched, the holes close completely without scarring, with re-growth of cartilage, and reappearance of both hair follicles and sebaceous glands. Studies using (MRL/lpr x C57BL/6)F2 and backcross mice first showed that this phenomenon was genetically determined and that multiple loci contributed to this quantitative trait. The lpr mutation itself, however, was not one of them. In the present study, we examined the genetic basis of healing in the Large (LG/J) mouse strain, a parent of the MRL mouse and a strain that shows the same healing phenotype. LG/J mice were crossed with Small (SM/J) mice and the F2 population was scored for healing and their genotypes determined at >200 polymorphic markers. As we previously observed for MRL and (MRL x B6) F2 mice, the wound healing phenotype was sexually dimorphic with female mice healing more quickly and more completely than male mice. We found quantitative trait loci (QTL) on chromosomes (chr) 9, 10, 11, and 15. The heal QTL on chrs 11 and 15 were linked to differential healing primarily in male animals, whereas QTL on chrs 9 and 10 were not sexually dimorphic. A comparison of loci identified in previous crosses with those in the present report using LG/J x SM/J showed that loci on chrs 9, 11 and 15 co-localized with those seen in previous MRL crosses, whereas the locus on chr 10 was not seen before and was is contributed by SM/J.
2009-07-27 | GSE17168 | GEO
Project description:Cryptorchidism and scrotal heating result in abnormal spermatogenesis but the mechanism(s) proscribing this temperature sensitivity are unknown. It was previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat resistant than the testis from the C57BL/6 strain. We have attempted to probe into the mechanism(s) involved in heat sensitivity by examining global gene expression profiles of normal and heat-treated testes from C57BL/6, AKR/N and MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and 416 transcripts were differentially expressed (at least two-fold higher or lower) when compared to the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts between them. There were 231 transcripts differentially expressed between C57BL/6 and two purported heat-resistant strains, AKR/N and MRL/MpJ-+/+.
2008-11-01 | GSE12950 | GEO
Project description:Cryptorchidism and scrotal heating result in abnormal spermatogenesis but the mechanism(s) proscribing this temperature sensitivity are unknown. It was previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat resistant than the testis from the C57BL/6 strain. We have attempted to probe into the mechanism(s) involved in heat sensitivity by examining global gene expression profiles of normal and heat-treated testes from C57BL/6, AKR/N and MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and 416 transcripts were differentially expressed (at least two-fold higher or lower) when compared to the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts between them. There were 231 transcripts differentially expressed between C57BL/6 and two purported heat-resistant strains, AKR/N and MRL/MpJ-+/+. Experiment Overall Design: Total RNA of testes from 3 different strains of mice, C57BL/6, AKR/N and MRL/MpJ-+/+, were analyzed using microarray 430.20 chip. All mice were 8 weeks old, 2 mice/strain.
2008-11-15 | E-GEOD-12950 | biostudies-arrayexpress
Project description:The MRL/MpJ mouse strain is known as a model of mammalian regeneration. The strain exhibits an unusual capacity in regenerative wound healing manifested by scarless ear-hole closure and enhanced regeneration response reported in other organs. A significant feature of the strain is that the adult MRL/MpJ mouse retains several embryonic biochemical characteristics, including increased expression of stem cell markers. As the regenerative response after injury is rather limited in mammals the MRL/MpJ mouse is a great model to study the molecular and cellular basis of scarless wound healing. We report here the analysis of genome-wide transcriptomic profiles in the heart, ear, spleen, liver and bone marrow of the MRL/MpJ mouse. We used gene expression microarray, which interrogates 44.170 of mouse transcripts, in order to identify the genes exhibiting remarkable differences in expression in the MRL/MpJ mouse compared to two reference strains: C57BL/6J and BALB/c. The comparison revealed hundreds of differentially expressed transcripts. Significant enrichments of genes engaged in retinol metabolism, peroxisome proliferator-activated receptor (PPAR), wound healing, and homeobox pathways distinguishes the differentially expressed transcripts up-regulated in the MRL/MpJ mouse, whereas the genes related to immune response, including including response to wounding are greatly enriched among those down-regulated. The same functional categories were associated with remarkable parallels between the transcriptomic patterns in murine neonates and the adult MRL/MpJ mouse.
2015-12-30 | GSE64624 | GEO
Project description:Femoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats; Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Previously, we identified that the region of 4q21-q41 on chromosome (Chr) 4 uniquely harbors multiple femoral neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW) rats. In this study we identified the candidate genes for femoral neck density and structure by correlating gene expression in the proximal femur with the femoral neck phenotypes linked to the QTLs on Chr 4. Microarray analysis was performed using RNA extracted from proximal femora of 4-week-old rats from F344, LEW and two other strains. A total of 104 genes in the 4q21-q41 region were differentially expressed (p<0.05) among all strains of rats with a false discovery rate (FDR) less than 10%. These 104 genes were then ranked based on the proportion of variation in femoral neck phenotypes in F2 animals homozygous for a particular strainâ??s allele at the Chr 4 QTL explained by the expression level of the gene in that strain. A total of 37 genes, including 21 candidate genes and 16 predicted genes, were strongly correlated (r2>0.50) with different femoral neck phenotypes and prioritized for further analysis. Ingenuity pathway analysis revealed several direct or indirect relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, interleukin 6, insulin growth factor 2, androgen receptor and tumor necrosis factor. Experiment Overall Design: Comparison of differentially expressed genes at the chromosome 4 QTL identified in F344 and LEW F2 rats.
2009-04-04 | E-GEOD-11180 | biostudies-arrayexpress
Project description:Animal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel antibody transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von-Willebrand-factor A like domain 2) transfer showed clear variability among inbred mouse strains; i.e. severe cutaneous blistering and inflammation in C57Bl/6J, and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57Bl/6J or MRL/MpJ mice showed an impaired ROS release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune-complex activated neutrophils from either C57Bl/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA. We used microarray to differentiate between the molecular response for the immune complex stimulated neutrophils in MRL/MpJ and C57Bl/6J mice To unravel the molecular basis for the different response to immune complex (IC) stimulation between MRL/MpJ and C57Bl/6J mice, the cells were activated using IC, and differential expression using microarray was compared between resting or activated neutrophils from MRL/MpJ or C57Bl/6J mice.
2015-06-24 | E-GEOD-70193 | biostudies-arrayexpress
Project description:Due to the limited capacity of mammals to regenerate complex tissues, researchers have worked to understand the mechanisms of tissue regeneration in organisms that maintain that capacity. One example is the MRL/MpJ mouse strain with unique regenerative capacity in ear pinnae that is absent from other strains, such as the common C57BL/6 strain. The MRL/MpJ mouse has also been associated with an autoimmune phenotype even in the absence of the mutant Fas gene described in its parent strain MRL/lpr. Due to these findings, we evaluated the differences between the responses of MRL/MpJ versus C57BL/6 strain in volumetric muscle injury and subsequent material implantation. One salient feature of the MRL/MpJ response to injury was robust adipogenesis within the muscle. This was associated with a decrease in M2-like polarization in response to biologically derived extracellular matrix scaffolds. In pro-fibrotic materials, such as polyethylene, there were fewer foreign body giant cells in the MRL/MpJ mice. As there are reports of both positive and negative influences of adipose tissue and adipogenesis on wound healing, this model could provide an important lens to investigate the interplay between stem cells, adipose tissue, and immune responses in trauma and material implantation.
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