The phenotype of the most common human ADAR1p150 Za domain mutation P193A in mice is incompletely penetrant
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA910555 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:ADAR1 mediated A-to-I RNA editing is a self/non-self discrimination mechanism for cellular double stranded RNAs. ADAR mutations are one cause of Aicardi-Goutières Syndrome, an inherited paediatric encephalopathy, classed as a “Type I interferonopathy”. The most common ADAR1 mutation is a proline 193 alanine (p.P193A) mutation, mapping to the ADAR1p150 isoform specific Za domain. We report the development of an independent murine P195A knock-in mouse, homologous to the human P193A mutation. The Adar1P195A/P195A mice are largely normal and the mutation is well tolerated. Contrasting with previous reports when the P195A mutation was compounded with an ADAR1 null allele (Adar1P195A/-), we find a partially penetrant phenotype, with approximately half the animals being runted with a shortened lifespan and the remaining animals normal. Severe runting and shortened survival of Adar1P195A/- animals were partly associated with the parental genotype. The P195A mutation is well tolerated in vivo and the loss of MDA5 is sufficient to completely rescue phenotypes in the Adar1P195A/- mice.
2023-02-13 | GSE220628 | GEO
Project description:ADAR1 mediated A-to-I RNA editing is a self/non-self discrimination mechanism for cellular double stranded RNAs. ADAR mutations are one cause of Aicardi-Goutières Syndrome, an inherited paediatric encephalopathy, classed as a "Type I interferonopathy". The most common ADAR1 mutation is a proline 193 alanine (p.P193A) mutation, mapping to the ADAR1p150 isoform specific Z domain. Here we report the development of an independent murine P195A knock-in mouse, homologous to human P193A. The Adar1P195A/P195A mice are largely normal and the mutation is well tolerated. When the P195A mutation is compounded with an Adar1 null allele (Adar1P195A/-), approximately half the animals are runted with a shortened lifespan while the remaining Adar1P195A/- animals are normal, contrasting with previous reports. The phenotype of the Adar1P195A/- animals is both associated with the parental genotype and partly non-genetic/environmental. Complementation with an editing deficient ADAR1 (Adar1P195A/E861A), or the loss of MDA5, rescues phenotypes in the Adar1P195A/- mice.
| S-SCDT-10_15252-EMBR_202255835 | biostudies-other
Project description:ADAR1 +/+ vs ADAR1 Za/Za HEK293 cells (deep-seq)
| PRJEB52618 | ENA
Project description:Genome-wide positions of Z-DNA are mapped. ChIP was performed against transiently expressing Flag-Za or Flag-Zaa using Flag antibody in HeLa cells. Za and Zaa ChIP DNA and fragmented genomic DNA were used for sequencing library construction. Each library was sequenced on Illumina GAIIx and HiSeq 2500 and sequenced reads were mapped and normalized.
2016-07-13 | GSE71682 | GEO
Project description:Cedecea colo strain:ZA Genome sequencing and assembly
| PRJNA526971 | ENA
Project description:In susceptible plant hosts, co-evolution has favoured viral strategies to evade host defenses and utilize resources to their own benefit. The degree of manipulation of host gene expression is dependent on host-virus specificity and certain abiotic factors. In order to gain insight into global transcriptomic changes for a geminivirus pathosystem, South African cassava mosaic virus [ZA:99] (SACMV-ZA:99]) and Arabidopsis thaliana, 4 x 44K Agilent microarrays were adopted. After normalization, a 2-fold change filtering of data (p<0.05) identified 1,820 differentially expressed genes in apical leaf tissue. A significant increase in differential gene expression over time (451 genes at 14 dpi, 742 genes at 24 dpi, and 1011 genes at 36 dpi) was observed. This increase in expression, correlated with an increase in SACMV accumulation as virus copies were 5-fold higher at 24 dpi and 6-fold higher at 36 dpi than at 14 dpi (1.1x104 virus copies present at 14 dpi, 5.7x104 copies at 24 dpi, and 6.3x104 copies at 36 dpi). Many 2-fold genes were primarily involved in stress and defense responses, phytohormone signalling pathways, cellular transport, cell-cycle regulation, transcription, oxidation-reduction, and other metabolic processes. Forty-one genes (2.3%) were shown to be continuously expressed across the infection period, indicating that the majority of genes were transient and unique to a particular time point. Plant signalling networks were disrupted and manipulated by SACMV-[ZA:99] in order to affect homeostasis and antagonize hostM-bM-^@M-^Ys defense responses. At the same time, an adaptive response was initiated to reprogramme metabolism and divert energy from growth-related processes to defense, all leading to disruption of normal biological host processes. Comparisons between SACMV-[ZA:99] with plant-infecting RNA and DNA viruses revealed similarities and differences in expression patterns among viruses, showing either general defense or virus-specific responses. Within the Geminiviridae family in particular, similarities in cell-cycle regulation and gene expression patterns correlated between SACMV-[ZA:99] and Cabbage leaf curl virus (CaLCuV) but differences were also evident. For instance, CaLCuV showed antagonistic interactions between Salicyclic Acid (SA) and Jasmonic Acid (JA) pathways, whereas SACMV displayed synergism. Differences in gene induction, repression and outcome between the two geminiviruses clearly demonstrated host-specific interactions with SACMV-[ZA:99] leading to infection. To our knowledge this is the first geminivirus study identifying differentially expressed transcripts across 3 time points A three time-point (14, 24, and 36 dpi) study was carried out to identify differentially expressed genes in SACMV-[ZA:99] infected Arabidopsis leaf cells using a direct comparison design against mock-inoculated controls. Three biological replicates and 1 technical replicate for both SACMV-[ZA:99]-infected and mock-inoculated controls were conducted at each time point.
2013-01-07 | E-GEOD-43282 | biostudies-arrayexpress
Project description:We report differential gene expression changes by benzyl isothiocyanate (BITC) and/or zoledronic acid (ZA) in MDA-MB-231 human breast cancer cell line
2023-05-31 | GSE233745 | GEO
Project description:In susceptible plant hosts, co-evolution has favoured viral strategies to evade host defenses and utilize resources to their own benefit. The degree of manipulation of host gene expression is dependent on host-virus specificity and certain abiotic factors. In order to gain insight into global transcriptomic changes for a geminivirus pathosystem, South African cassava mosaic virus [ZA:99] (SACMV-ZA:99]) and Arabidopsis thaliana, 4 x 44K Agilent microarrays were adopted. After normalization, a 2-fold change filtering of data (p<0.05) identified 1,820 differentially expressed genes in apical leaf tissue. A significant increase in differential gene expression over time (451 genes at 14 dpi, 742 genes at 24 dpi, and 1011 genes at 36 dpi) was observed. This increase in expression, correlated with an increase in SACMV accumulation as virus copies were 5-fold higher at 24 dpi and 6-fold higher at 36 dpi than at 14 dpi (1.1x104 virus copies present at 14 dpi, 5.7x104 copies at 24 dpi, and 6.3x104 copies at 36 dpi). Many 2-fold genes were primarily involved in stress and defense responses, phytohormone signalling pathways, cellular transport, cell-cycle regulation, transcription, oxidation-reduction, and other metabolic processes. Forty-one genes (2.3%) were shown to be continuously expressed across the infection period, indicating that the majority of genes were transient and unique to a particular time point. Plant signalling networks were disrupted and manipulated by SACMV-[ZA:99] in order to affect homeostasis and antagonize host’s defense responses. At the same time, an adaptive response was initiated to reprogramme metabolism and divert energy from growth-related processes to defense, all leading to disruption of normal biological host processes. Comparisons between SACMV-[ZA:99] with plant-infecting RNA and DNA viruses revealed similarities and differences in expression patterns among viruses, showing either general defense or virus-specific responses. Within the Geminiviridae family in particular, similarities in cell-cycle regulation and gene expression patterns correlated between SACMV-[ZA:99] and Cabbage leaf curl virus (CaLCuV) but differences were also evident. For instance, CaLCuV showed antagonistic interactions between Salicyclic Acid (SA) and Jasmonic Acid (JA) pathways, whereas SACMV displayed synergism. Differences in gene induction, repression and outcome between the two geminiviruses clearly demonstrated host-specific interactions with SACMV-[ZA:99] leading to infection. To our knowledge this is the first geminivirus study identifying differentially expressed transcripts across 3 time points
2013-01-07 | GSE43282 | GEO
Project description:Adar +/- vs Adar Za/- primary lung fibroblasts
| PRJEB52610 | ENA
Project description:uncultured crAssphage strain:ZA | isolates :M186D4, C0521BW15,C0526BW15, C0521BD4, and C0531BW4
| PRJNA526942 | ENA