The Wilms tumor-suppressor gene WT1, a key player in renal development, also has a crucial role in maintenance of the glomerulus in the mature kidney. However, molecular pathways orchestrated by WT1 in podocytes, where it is highly expressed, remain unknown. Their defects are thought to modify the cross-talk between podocytes and other glomerular cells and ultimately lead to glomerular sclerosis, as observed in diffuse mesangial sclerosis (DMS) a nephropathy associated with WT1 mutations.
A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Sex, Specimen part
View SamplesPreviously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viral families. How the picornaviral RdRP transgene exerted antiviral protection in vivo was not known. To investigate the molecular mechanism, we determined gene expression profiles in spinal cords of WT and RdRP transgenic mice prior to (baseline) and after (2 days) infection with Encephalomyocarditis Virus (EMCV).
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Sex
View SamplesPreviously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viruses. Using mouse genetic studies, we determined that uninfected RdRP transgenic mice inherently induce an arsenel of prominent antiviral effectors and that this phenotype is MDA5-, MAVS- and IFNR-dependent. To determine the mechanism underlying MDA5 activation and induction of constitutive antiviral signaling by the picornaviral RdRP, we constructed mutant RdRP transgenes. First, we introduced pervasive, coding-neutral point mutations into the RdRP cDNA to maximally disrupt primary and secondary RNA structure (RdRPrna). Another mutant, RdRPcat, lacks catalytic activity due to alanine substitution of the key catalytic center triad aspartate residues (D233, D328, and D329), but is otherwise intact at the nucleotide and amino acid levels. The WT, RdRPrna, and RdRPcat versions of the RdRP transgenes were transduced with lentiviral vectors into human THP-1 monocytes, with RdRP mRNA transcription controlled by the Spleen Focus Forming Virus (SFFV) promoter. In parallel a control cell line transduced with a vector lacking any RdRP transgene (null THP-1) was generated.
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Specimen part
View SamplesPreviously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viruses. Using mouse genetic studies, we determined that uninfected RdRP transgenic mice inherently induce an arsenel of prominent antiviral effectors and that this phenotype is MDA5-, MAVS- and IFNR-dependent. To determine the mechanism underlying MDA5 activation and induction of constitutive antiviral signaling by the picornaviral RdRP, we constructed mutant RdRP transgenes. First, we introduced pervasive, coding-neutral point mutations into the RdRP cDNA to maximally disrupt primary and secondary RNA structure (RdRPrna). Another mutant, RdRPcat, lacks catalytic activity due to alanine substitution of the key catalytic center triad aspartate residues (D233, D328, and D329), but is otherwise intact at the nucleotide and amino acid levels. The WT, RdRPrna, and RdRPcat versions of the RdRP transgenes were transduced with lentiviral vectors into human THP-1 monocytes, with RdRP mRNA transcription controlled by the Spleen Focus Forming Virus (SFFV) promoter. In parallel a control cell line transduced with a vector lacking any RdRP transgene (null THP-1) was generated.
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Specimen part
View SamplesPreviously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viruses. Using mouse genetic studies, we determined that uninfected RdRP transgenic mice inherently induce an arsenel of prominent antiviral effectors and that this phenotype is MDA5-, MAVS- and IFNR-dependent. To determine the mechanism underlying MDA5 activation and induction of constitutive antiviral signaling by the picornaviral RdRP, we constructed mutant RdRP transgenes. First, we introduced pervasive, coding-neutral point mutations into the RdRP cDNA to maximally disrupt primary and secondary RNA structure (RdRPrna). Another mutant, RdRPcat, lacks catalytic activity due to alanine substitution of the key catalytic center triad aspartate residues (D233, D328, and D329), but is otherwise intact at the nucleotide and amino acid levels. The WT, RdRPrna, and RdRPcat versions of the RdRP transgenes were transduced with lentiviral vectors into human THP-1 monocytes, with RdRP mRNA transcription controlled by the Spleen Focus Forming Virus (SFFV) promoter. In parallel a control cell line transduced with a vector lacking any RdRP transgene (null THP-1) was generated.
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Specimen part
View SamplesPreviously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viral families. How the picornaviral RdRP transgene exerted antiviral protection in vivo was not known. To investigate the molecular mechanism, we determined gene expression profiles in spinal cords of WT and RdRP transgenic mice prior to (baseline) and after (2 days) infection with Encephalomyocarditis Virus (EMCV).
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Sex
View SamplesPreviously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viral families. How the picornaviral RdRP transgene exerted antiviral protection in vivo was not known. To investigate the molecular mechanism, we determined gene expression profiles in spinal cords of WT and RdRP transgenic mice prior to (baseline) and after (2 days) infection with Encephalomyocarditis Virus (EMCV).
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sex, Specimen part
View SamplesWe are using genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs.
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sex, Specimen part
View Samples