Intersection of Immunity, Metabolism, and Muscle Regeneration in an Autoimmune-Prone MRL Mouse Model
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE252436 | GEO | 2024/01/08
REPOSITORIES: GEO
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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: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: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:Epigenetic regulation plays essential role in cell differentiation and dedifferentiation, which are the intrinsic processes involved in regeneration. In order to investigate the epigenetic basis of regeneration capacity, we choose DNA methylation as one of the most important epigenetic mechanisms and the MRL/MpJ mouse as a model of mammalian regeneration reported to exhibit enhanced regeneration response in different organs. We report the comparative analysis of genomic DNA methylation profiles of the MRL/MpJ and the control C57BL/6J mouse. Methylated DNA immunoprecipitation (MeDIP) followed by microarray analysis using Nimblegen M-bM-^@M-^\3x720K CpG Island Plus RefSeq PromoterM-bM-^@M-^] platform were applied in order to carry out genome-wide DNA methylation profiling covering 20,404 promoter regions. We identified hundreds of hypo- and hypermethylated genes and CpG islands in heart, liver and spleen, and 37 of them in the three tissues. Decreased inter-tissue diversification and the shift of DNA methylation balance upstream the genes distinguish the genomic methylation patterns of the MRL/MpJ mouse from the C57BL/6J. Homeobox genes and a number of other genes involved in embryonic morphogenesis are significantly over-represented among the genes hypomethylated in the MRL/MpJ mouse. These findings indicate that epigenetic patterning might be a likely molecular basis of regeneration capability in the MRL/MpJ mouse. genome-wide DNA methylation profiling in the heart, liver, and spleen tissues of MRL/MpJ and C57BL/6J mouse
2013-08-20 | E-GEOD-49221 | biostudies-arrayexpress
Project description:Epigenetic regulation plays essential role in cell differentiation and dedifferentiation, which are the intrinsic processes involved in regeneration. In order to investigate the epigenetic basis of regeneration capacity, we choose DNA methylation as one of the most important epigenetic mechanisms and the MRL/MpJ mouse as a model of mammalian regeneration reported to exhibit enhanced regeneration response in different organs. We report the comparative analysis of genomic DNA methylation profiles of the MRL/MpJ and the control C57BL/6J mouse. Methylated DNA immunoprecipitation (MeDIP) followed by microarray analysis using Nimblegen “3x720K CpG Island Plus RefSeq Promoter” platform were applied in order to carry out genome-wide DNA methylation profiling covering 20,404 promoter regions. We identified hundreds of hypo- and hypermethylated genes and CpG islands in heart, liver and spleen, and 37 of them in the three tissues. Decreased inter-tissue diversification and the shift of DNA methylation balance upstream the genes distinguish the genomic methylation patterns of the MRL/MpJ mouse from the C57BL/6J. Homeobox genes and a number of other genes involved in embryonic morphogenesis are significantly over-represented among the genes hypomethylated in the MRL/MpJ mouse. These findings indicate that epigenetic patterning might be a likely molecular basis of regeneration capability in the MRL/MpJ mouse.
2013-08-20 | GSE49221 | GEO
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: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
2015-06-24 | GSE70193 | GEO
Project description:Previous studies have suggested that the heart may be capable of limited repair and regeneration in response to a focal injury while other studies indicate that the mammalian heart has no regenerative capacity. To further explore this issue, we performed a series of superficial and transmural myocardial injuries in C57BL/6 and MRL/MpJ adult mice. At defined time intervals following the respective injury (Days 3, 14, 30 and 60) we examined cardiac function using echocardiography, morphology, FACS cell sorting for BrdU positive cells and molecular signature using microarray analysis. We observed complete restoration of myocardial function in the superficial MRL cryoinjured heart and significantly less scar formation as compared to the injured hearts of C57BL/6 mice. Following a severe transmural myocardial injury, the MRL mouse has increased survival and decreased ventricular remodeling compared to the C57BL/6 mouse but without evidence of significant regeneration. The cytoprotective program observed in the severely injured MRL heart is in part due to increased vasculogenesis and decreased apoptosis that limits the extension of the injury. We conclude that C57BL/6 and MRL injured hearts have evidence of limited myocardial regeneration, in response to superficial injury, but the improved function and survival observed in the MRL mouse heart following severe injury is not due to significant regenerative processes. Mouse hearts from C57BL/6 and MRL/MpJ strains were injured with LAD ligation and harvested at 3, 30 and 60 days after treatement.
2007-11-23 | E-GEOD-4710 | biostudies-arrayexpress
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-+/+. Next, the testes of C57BL/6 and AKR/N mice were exposed to 43ºC for 15 min and harvested at different time points for TUNEL studies and microarrays. An increase of TUNEL-positive germ cell numbers was significant 8 hr after heat exposure in the C57BL/6 mouse. However, this increase was not observed in the AKR/N mouse until 10 hr after heat exposure. All tubules showed germ cell loss and disruption in C57BL/6 testis 24 hr after heat shock. In contrast, although a number of seminiferous tubules showed an abnormal morphology 24 hr post-heat shock in the AKR/N mouse, many tubules still retained a normal structure. Numerous transcripts exhibited differential regulation between the two strains within 24 hours after heat exposure. The differentially expressed transcripts in the testes 8 hr after heat exposure were targeted to identify the genes involved in the initial response rather than those due to germ cell loss. Twenty transcripts were significantly down-regulated and 19 genes were up-regulated by hyperthermia in C57BL/6 and did not show a parallel change in the AKR/N testis. Conversely, heat shock resulted in 30 up-regulated transcripts and 31 down-regulated transcripts in AKR/N that were not similarly regulated in C57BL/6. A number of genes shared similar differential expression patterns and differential regulation by hyperthermia in both strains of mice. Taken together, the present study indicates the diverse genetic backgrounds in the three strains lead to major differences in normal testis gene expression profiles while the differences in heat shock responses involves a significantly smaller number of genes. The data generated may provide insights regarding gene networks and pathways involved in heat stress and their relationship to spermatogenesis.
2008-11-01 | GSE13010 | GEO
Project description:The aim of the study was to find genomic regions that show differences in DNA methylation status between the MRL/MpJ mouse, which show enhanced regeneration response, and two control mouse strains C57BL/6J and BALB/c.
2017-11-03 | GSE89518 | GEO