Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA271887 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Ectopic calcification in synovial tissues is devastating to diarthrodial joints. While some forms of synovial ectopic calcification have genetically simple basis, most cases manifest as complex traits with environmental and multigenic components. The location of causal loci or the physiological processes affected by allelic variants is poorly understood. Here, we report on genetic susceptibility to ectopic calcification in the LG/J and SM/J advanced intercross mice. Using 347 mice in 98 full-sibships, destabilization of medial meniscus was performed to induce joint injury. We performed quantitative trait locus (QTL) analysis to map calcification phenotypes to discrete genomic locations. To validate the functional significance of the selected QTL candidate genes, we compared mRNA expression between parental LG/J and SM/J inbred strains. Our findings showed that joint destabilization instigated ectopic calcifications as detected and quantified by micro-CT. Overall, we detected 20 QTLs affecting synovial and meniscus calcification phenotypes with 11 QTLs linked to synovial calcification. Functional and bioinformatic analyses of single nucleotide polymorphism identified functional classifications relevant to angiogenesis (Myo1e, Kif26b, Nprl3, Stab2, Fam105b), bone metabolism/calcification (Tle3, Tgfb2, Lipc, Nfe2l1, Ank, Fam105b), arthritis (Stab2, Tbx21, Map4k4, Hoxb9, Larp6, Col1a2, Adam10, Timp3, Nfe2l1, Trpm3), and ankylosing-spondylitis (Ank, Pon1, Il1r2, Tbkbp1) indicating that ectopic calcification involves multiple mechanisms. Furthermore, the expression of 11 candidate genes was significantly different between LG/J and SM/J. Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with synovial calcification. Our findings of multiple genetic loci affecting the phenotype suggest the involvement of multiple genes contributing to its pathogenesis. We collected tissue lysates from the formalin-fixed paraffin-embedded sections from mouse knee joints and analyzed the expression of several genes by Affymetrix QuantiGene Plex assay.
2015-01-09 | E-GEOD-64793 | biostudies-arrayexpress
Project description:Ectopic calcification in synovial tissues is devastating to diarthrodial joints. While some forms of synovial ectopic calcification have genetically simple basis, most cases manifest as complex traits with environmental and multigenic components. The location of causal loci or the physiological processes affected by allelic variants is poorly understood. Here, we report on genetic susceptibility to ectopic calcification in the LG/J and SM/J advanced intercross mice. Using 347 mice in 98 full-sibships, destabilization of medial meniscus was performed to induce joint injury. We performed quantitative trait locus (QTL) analysis to map calcification phenotypes to discrete genomic locations. To validate the functional significance of the selected QTL candidate genes, we compared mRNA expression between parental LG/J and SM/J inbred strains. Our findings showed that joint destabilization instigated ectopic calcifications as detected and quantified by micro-CT. Overall, we detected 20 QTLs affecting synovial and meniscus calcification phenotypes with 11 QTLs linked to synovial calcification. Functional and bioinformatic analyses of single nucleotide polymorphism identified functional classifications relevant to angiogenesis (Myo1e, Kif26b, Nprl3, Stab2, Fam105b), bone metabolism/calcification (Tle3, Tgfb2, Lipc, Nfe2l1, Ank, Fam105b), arthritis (Stab2, Tbx21, Map4k4, Hoxb9, Larp6, Col1a2, Adam10, Timp3, Nfe2l1, Trpm3), and ankylosing-spondylitis (Ank, Pon1, Il1r2, Tbkbp1) indicating that ectopic calcification involves multiple mechanisms. Furthermore, the expression of 11 candidate genes was significantly different between LG/J and SM/J. Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with synovial calcification. Our findings of multiple genetic loci affecting the phenotype suggest the involvement of multiple genes contributing to its pathogenesis.
2015-01-09 | GSE64793 | GEO
Project description:Genetic loci that regulate healing and regeneration in LG/J and SM/J mice
| PRJNA119761 | ENA
Project description:Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate the efficacy of long-term oral K3Citrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. K3Citrate successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion. Notably, a positive effect on grip strength, a marker of frailty, was evident in treated mice. Spectroscopic investigation of the persisting calcified nodules indicated K3Citrate did not alter the mineral composition, and collagen 10 and aggrecan staining revealed that reactivation of an endochondral differentiation program in endplates may drive LG/J disc calcification. Importantly, K3Citrate reduced calcification incidence without altering the abundance of endplate hypertrophic chondrocytes, suggesting mitigation of disc calcification through Ca2+ chelation. This was further supported by the inability of K3Citrate to inhibit hypertrophic differentiation of chondrogenic ATDC5 cells and minimal effects on their metabolic status. Overall, this study sheds light on the pathogenesis of intervertebral disc calcification in LG/J mice and underscores the therapeutic potential of K3Citrate as a systemic intervention strategy for disc calcification.
2024-08-16 | GSE270561 | 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:Treatment of oocytes derived from large (4-6 mm; LG) or small (>3 mm; SM) follicles with glial cell line-derived neurotrophic factor (GDNF) during in vitro maturation. Four-condition experiment, SM and LG oocytes, each with and without GDNF. Biological replicates: 9 per condition, independently collected. Pools of three replicates per array.
2012-11-09 | E-GEOD-42198 | biostudies-arrayexpress
Project description:Objectives: Understanding the molecular mechanisms underlying cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). We report transcripts and pathways differentially expressed in chondrocytes obtained from genotypically and phenotypically distinct mouse strains. Methods: We performed RNA-sequencing and computational analysis on chondrocytes derived from LG/J (large, healer, n=16) and SM/J (small, non-healer, n=16) mouse strains. We validated the expression of candidate genes using real-time PCR and immunostaining. Results: Of those nearly 6,000 differentially expressed genes between LG/J and SM/J, 138 genes (99 protein-coding) were up-regulated and 145 (103 protein-coding) were down-regulated with log2 fold changes of 2 or more. Interestingly, we found the top up-regulated gene ontology biological pathways in the chondrocytes from the LG/J mice were related to chondrocyte development, cartilage condensation, and regulation of chondrocyte differentiation. In contrast, the top upregulated pathways in the SM/J mice were mostly inflammation related. Real-time PCR confirmed the expression pattern of a number of differentially expressed genes. Immunostaining of two candidate genes revealed that Tnfrsf23 and Car2 were respectively increased in LG/J and SM/J strains. Conclusions: The enrichment of genes and pathways related chondrocyte differentiation, cartilage development and cartilage condensation in LG/J appear to be responsible for their superior healing potential. The enrichment of pathways related to cytokine production, immune cell activation and inflammation in SM/J suggests a compromised chondrocyte proliferation and/or survival ability and a higher sensitivity to inflammation and OA. Tnfrsf23 and Car2 warrant further investigation to discern their specific role(s) in chondrocyte function and OA.
2020-03-17 | GSE128490 | GEO
Project description:Treatment of oocytes derived from large (4-6 mm; LG) or small (>3 mm; SM) follicles with glial cell line-derived neurotrophic factor (GDNF) during in vitro maturation.
2012-11-09 | GSE42198 | GEO
Project description:To fully apprehend the complex mechanisms responsible for intervertebral disc (IVD) degeneration, one needs to gain a deeper understanding of what characterizes a good and bad intervertebral disc. Using a quantitative proteomic approach, we compared methodically the differences existing between a mouse model known as good healer LG/J to another mouse model characterize as bad healer SM/J. A total of 5245 proteins were identified. By assessing the overlap of the NP LG/J and SM/J proteomic signature with a list of over 1000 matrisomal proteins generated by Naba and co-workers (33), we provide a first comprehensive comparison of NP IVD matrix composition in a good and bad condition and identify potential changes that are fundamental for maintenance of a healthy disc.
2018-04-16 | PXD008784 | Pride