129-derived passenger mutations confound phenotype of ACKR1-deficient mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1077396 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A majority of genetically modified mice carry passenger mutations, originating from the 129-derived embryonic stem (ES) cells, near the targeted gene. Unintended retention of these mutations can introduce confounding phenotypes and affect conclusions. We show that Ackr1-/-129ES mice retained approximately 6 Mb of 129 ES cells-derived genomic material in chromosome 1 near Ackr1 in bone marrow derived monocytes (Mono), nucleated erythroblasts (NECs), and polymorphonucleated neutrophils (PMN), notably affecting the expression of PYHIN genes.
2024-09-15 | GSE256021 | GEO
Project description:The Toll/IL-1R-domain-containing adaptor protein SARM1 is expressed primarily in the brain, where it mediates axonal degeneration. Roles for SARM1 in TLR signaling, viral infection, inflammasome activation, and chemokine and Xaf1 expression have also been described. Much of the evidence for SARM1 function relies on SARM1-deficient mice generated in 129 ESCs and backcrossed to B6. The Sarm1 gene lies in a gene-rich region encompassing Xaf1 and chemokine loci, which remain 129 in sequence. We therefore generated additional knockout strains on the B6 background, confirming the role of SARM1 in axonal degeneration and WNV infection, but not in VSV or LACV infection, or in chemokine or Xaf1 expression. Sequence variation in proapoptotic Xaf1 between B6 and 129 results in coding changes and distinct splice variants, which may account for phenotypes previously attributed to SARM1. Reevaluation of phenotypes in these strains will be critical for understanding the function of SARM1.
| S-EPMC7226674 | biostudies-literature
Project description:Targeted mutagenesis in mice is a powerful tool for functional analysis of genes. However, genetic variation between embryonic stem cells (ESCs) used for targeting (previously almost exclusively 129-derived) and recipient strains (often C57BL/6J) typically results in congenic mice in which the targeted gene is flanked by ESC-derived passenger DNA potentially containing mutations. Comparative genomic analysis of 129 and C57BL/6J mouse strains revealed indels and single nucleotide polymorphisms resulting in alternative or aberrant amino acid sequences in 1,084 genes in the 129-strain genome. Annotating these passenger mutations to the reported genetically modified congenic mice that were generated using 129-strain ESCs revealed that nearly all these mice possess multiple passenger mutations potentially influencing the phenotypic outcome. We illustrated this phenotypic interference of 129-derived passenger mutations with several case studies and developed a Me-PaMuFind-It web tool to estimate the number and possible effect of passenger mutations in transgenic mice of interest.
| S-EPMC4800811 | biostudies-literature
Project description:Experiment 2 - MiRNA mimics have a length and passenger strand specific effect Wildtype and mutant variants of miR-155 and negative control miRNA mimics were transfected to address the phenotype
2015-12-09 | GSE75801 | GEO
Project description:1 year-old male Tenascin-C deficient 129/SV mice with the targeted insertion of a beta-lactamase cassette in the NcoI site of exon 2 of the TNC gene (Forsberg, E., Hirsch, E., Frohlich, L., Meyer, M., Ekblom, P., Aszodi, A., Werner, S. & Fassler, R. (1996) Proc. Natl. Acad. Sci U. S. A 93, 6594-6599) were used for the study. Animals were derived from the original strain and back-crossed with wildtype 129/SV mice (Institut für Labortierkunde, University of Zurich). Animals were acclimatized to housing in single cages for one week. Soleus muscle was harvested, total RNA isolated and subjected to transcript profiling with custom microarrays with custom-designed ATLASTM cDNA nylon filter as described (Dapp, C., Schmutz, S., Hoppeler, H. & Fluck, M. (2004) Physiol Genomics 20, 97-107). Keywords: Transcriptome
2008-08-08 | GSE8550 | GEO
Project description:1 year-old male Tenascin-C deficient 129/SV mice with the targeted insertion of a beta-lactamase cassette in the NcoI site of exon 2 of the TNC gene (Forsberg, E., Hirsch, E., Frohlich, L., Meyer, M., Ekblom, P., Aszodi, A., Werner, S. & Fassler, R. (1996) Proc. Natl. Acad. Sci U. S. A 93, 6594-6599) were used for the study. Animals were derived from the original strain and back-crossed with wildtype 129/SV mice (Institut für Labortierkunde, University of Zurich). Animals were acclimatized to housing in single cages for one week followed by 7 days of hindlimb suspension and one day of reloading. Soleus muscle was harvested, total RNA isolated and subjected to transcript profiling with custom microarrays with custom-designed ATLASTM cDNA nylon filter as described (Dapp, C., Schmutz, S., Hoppeler, H. & Fluck, M. (2004) Physiol Genomics 20, 97-107). Keywords: Transcriptome
2008-08-08 | GSE8551 | GEO
Project description:Primary cilium serves as a cellular “antenna” to sense environmental signals. Ciliogenesis requires the removal of CP110 to convert the mother centriole into the basal body. Actin dynamics is also critical for cilia formation. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in the vertebrates, controlled cilia assembly by down-regulating both CP110 and four proteins critical for actin dynamics, Arp2, Toca1, abLIM1, and abLIM3. Consistently, blocking miR-129-3p repressed cilia formation in cultured mammalian cells, whereas its overexpression potently induced ciliogenesis in proliferating cells and extraordinary cilia elongation. Moreover, inhibition of miR-129-3p in zebrafish embryos suppressed cilia assembly in the Kupffer’s vesicle and pronephric duct, leading to developmental abnormalities including curved body, pericardial oedema, and randomised left-right patterning. Our results thus unravel a novel mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly via microRNA-mediated posttranscriptional regulations. We want to find the targets of miR-129-3p by overexpressing miR-129-3p oligo or control oligo in hTERT-RPE1 cells. Through microarray analysis we could check the downregulated genes and these genes might be the targets of miR-129-3p.
2012-06-01 | GSE34846 | GEO
Project description:Experiment 2 - MiRNA mimics have a length and passenger strand specific effect Wildtype and mutant variants of miR-155 and negative control miRNA mimics were transfected to address the phenotype Cells were transfected with mimics and samples were collected in duplicate (except 23mer miR-155 wild type mimic and 23mer negative control mimic)
2015-12-09 | E-GEOD-75801 | biostudies-arrayexpress
Project description:Transcriptome analysis of hindlimb muscles from dystrophic mice. The mdx mouse is a good genetic and molecular murine model for Duchenne Muscular Dystrophy (DMD), a progressive and devastating muscle disease. However, this model is inappropriate for testing new therapies due to its mild phenotype. Here, we transferred the mdx mutation to the 129/Sv strain with the aim to create a more severe model for DMD. Unexpectedly, functional analysis of the first three generations of mdx129 showed a progressive amelioration of the phenotype, associated to less connective tissue replacement, and more regeneration than the original mdxC57BL. Transcriptome comparative analysis was performed to identify what is protecting this new model from the dystrophic characteristics. The mdxC57BL presents three times more differentially expressed genes (DEGs) than the mdx129 (371 and 137 DEGs, respectively). However, both models present more overexpressed genes than underexpressed, indicating that the dystrophic and regenerative alterations are associated with the activation rather than repression of genes. As to functional categories, the DEGs of both mdx models showed a predominance of immune system genes. Excluding this category, the mdx129 model showed a decreased participation of the endo/exocytic pathway and homeostasis categories, and an increased participation of the extracellular matrix and enzymatic activity categories. Spp1 gene overexpression was the most significant DEG exclusively expressed in the mdx129 strain. This was confirmed through relative mRNA analysis and osteopontin protein quantification. The amount of the 66 kDa band of the protein, representing the post-translational product of the gene, was about 4.8 times higher on Western blotting. Spp1 is a known DMD prognostic biomarker, and our data indicate that its upregulation can benefit phenotype. Modeling the expression of the DEGs involved in the mdx mutation with a benign course should be tested as a possible therapeutic target for the dystrophic process. We analyzed calf muscles from five Dmdmdx, three hybrids of Dmdmdx with 129/Sv in generations F1, F2 and F3; five C57BL/6 and three 129/Sv as normal controls. All animals were six months old. We used the Affymetrix Mouse Gene 1.0 ST platform. Array data was processed by Expression Console. No technical replicates were performed.
2016-07-24 | E-GEOD-77126 | biostudies-arrayexpress
Project description:Bradyrhizobium diazoefficiens USDA 129 genome sequencing
| PRJNA1115737 | ENA