Liver p53-dependent gene expression 48hrs after Mdm2Ex5/6Δ (Mdm2tm2.1Glo) allele activation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE183082 | GEO | 2021/10/08
REPOSITORIES: GEO
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Project description:Liver p53-dependent gene expression 48hrs after Mdm2Ex5/6Δ (Mdm2tm2.1Glo) allele activation
| PRJNA759128 | ENA
Project description:DYT1 dystonia is a neurological movement disorder characterized by a dominant 3-base pair deletion (dGAG) in the TOR1A gene. This study demonstrates a gene editing approach that selectively targets the dGAG mutation in the TOR1A DYT1 allele while safeguarding the wild-type (WT) TOR1A allele. We optimized an adeno-associated virus (AAV) vector-compatible variant of the Staphylococcus aureus Cas9 nuclease ortholog (SaCas9-KKH) in DYT1 patient-derived human neuroprecursor cells (hNPCs). On-target editing of the TOR1A DYT1 allele was confirmed at the genomic level from brain tissue in a xenograft mouse model. To avoid brain biopsy for demonstrating TOR1A DYT1 editing, we developed a non-invasive monitoring method using extracellular RNA (exRNA). TOR1A exRNA was retrieved from the EV secretions of hNPCs and plasma samples, indicating whether the donor was a TOR1A DYT1 carrier. This technique enabled us to assess AAV-mediated disruption of the TOR1A DYT1 allele in the brains of mice using blood samples
2025-03-01 | GSE288087 | GEO
Project description:Comparison of gene expression in livers of either WT mice or mice with hepatic specific deletion of the gene Tribbles1. Animal groups were both Trib1 cKO mice homozygous for a floxed allele of Trib1. Mice aged 8-10 weeks were treated with adeno associated virus (AAV) encoding Cre recombinase (AAV_Cre) or no gene (AAV_null). The WT group is mice treated with AAV_Null, the liver-specific KO group treated with AAV_Cre. Gene expression data was then used in Ingenuity Pathway analysis to attempt to identify upstream transcription factors that might be responsible for the gene expression changes observed. All animals were 8-10 weeks of age, and all animals were homozygous for the floxed allele of Trib1. WT animals were treated with AAV_Null, Trib1 liver specific KO mice were treated with AAV_Cre. Mice were euthanized at 1-week post injection of AAV, and RNA collected from whole liver tissue.
2015-07-14 | E-GEOD-70846 | biostudies-arrayexpress
Project description:Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. GABRA1 encodes for the α1 subunit of the gamma-aminobutyric acid type A receptor (GABAAR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have previously been developed to understand the mechanism by which mutations in GABRA1 cause disease, but these models have produced complex and at times incongruent data. Thus, additional model systems are required to validate and substantiate previously published results. We investigated the behavioral patterns associated with a nonsense mutation of the zebrafish gabra1 (sa43718 allele) gene. The sa43718 allele causes a decrease in gabra1 mRNA expression, which is associated with light induced hypermotility, a phenotype indicative of seizure like behavior in zebrafish. Mutation of gabra1 was accompanied by decreased mRNA expression of gabra2, gabra3, and gabra5, indicating a reduction in the expression of additional alpha sub-units of the GABAAR. Although multiple sub-units were decreased in total expression, larvae continued to respond to pentylenetetrazole (PTZ) indicating that residual GABAARs exist in gabra1 homozygous mutants. Interestingly, shotgun (bottom-up) proteomics of whole brain larval homogenates demonstrated that loss of gabra1 function is associated with abnormal expression of proteins that regulate proton transport, ion homeostasis, vesicle transport, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the gabra1 gene result in seizure like phenotypes with abnormal function of inhibitory synapses.
2025-07-14 | PXD045670 | Pride
Project description:Palb2 interacts with BRCA1 and BRCA2 in supercomplexes involved in DNA repair via homologous recombination. Heterozygous germline mutations in PALB2 confer a moderate risk of breast cancer while biallelic PALB2 mutations are linked to a severe form of Fanconi anaemia characterized by early childhood solid tumours and severe chromosomal instability. In contrast to BRCA1- or BRCA2-associated cancers, breast tumours in heterozygous PALB2 mutation carriers do not show loss of the wild type allele, suggesting PALB2 might be haploinsufficient for tumour suppression. To study the role of PALB2 in development and tumourigenesis, we have generated Palb2GT mouse mutants using a gene trap approach. Whereas Palb2GT/GT homozygous mutant embryos died at mid-gestation due to massive apoptosis, Palb2GT/+ heterozygous mice were viable and did not show any obvious abnormalities. Deletion of p53 alleviated the phenotype of Palb2GT/GT embryos, but did not rescue embryonic lethality. In addition, loss of p53 did not significantly collaborate with Palb2 heterozygosity in tumourigenesis in heterozygous or homozygous p53 knockout mice. Tumours arising in Palb2GT/+;p53+/– or Palb2GT/+;p53–/– compound mutant mice retained the wild type Palb2 allele and did not display increased genomic instability.
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Project description:The metastasis associated (MTA) proteins, encoded in mammals by three highly similar gene paralogs, Mta1, Mta2, and Mta3, are integral components of the nucleosome remodeling deacetylase (NuRD) complex. While biochemical and molecular studies have probed the functions of the Mta gene family, genetic data in animals is less complete. Here we report the creation of a novel allele of Mta3 in which the first two coding exons, which encode the bromo-adjacent homology (BAH) domain of Mta3, are deleted. Animals homozygous for this Mta3DBAH allele are viable, fertile, and have no obvious deleterious phenotype. Exploration of the Mta3DBAH allele revealed that the Mta3 locus has an unannotated promoter located between Mta3 exons 3 and 4, which is unperturbed in the Mta3DBAH allele, which appears to drive expression of an MTA3 protein variant lacking the BAH domain. To explore the genetic relationship of this allele to the paralog Mta1, the Mta3DBAH animals were crossed to animals bearing the Mta1tm1a(EUCOMM)Wtsi allele, no double homozygous mutant animals were recovered, indicating synthetic lethality between these two Mta alleles. To understand the impact of the Mta3DBAH allele on functions previously described ex vivo, studies were performed to examine roles of Mta3 in the immune response and in androgen biology. Mta3DBAH homozygous animals have modest defects in B lymphocyte activation and antibody production, which could result in a selective disadvantage in a natural environment. Conditional mutation in B lymphocytes revealed selection for cells escaping deletion in post germinal center stages of antigen-dependent activation. No genetic requirements for Mta3 in androgen biology in adults were documented, but mutant animals display behavior defects consistent with altered androgen levels during early postnatal life. These studies clarify the genetic requirements for MTA proteins in mammalian development and identify specific functions for MTA3.
2025-07-24 | GSE297536 | GEO
Project description:Palb2 interacts with BRCA1 and BRCA2 in supercomplexes involved in DNA repair via homologous recombination. Heterozygous germline mutations in PALB2 confer a moderate risk of breast cancer while biallelic PALB2 mutations are linked to a severe form of Fanconi anaemia characterized by early childhood solid tumours and severe chromosomal instability. In contrast to BRCA1- or BRCA2-associated cancers, breast tumours in heterozygous PALB2 mutation carriers do not show loss of the wild type allele, suggesting PALB2 might be haploinsufficient for tumour suppression. To study the role of PALB2 in development and tumourigenesis, we have generated Palb2GT mouse mutants using a gene trap approach. Whereas Palb2GT/GT homozygous mutant embryos died at mid-gestation due to massive apoptosis, Palb2GT/+ heterozygous mice were viable and did not show any obvious abnormalities. Deletion of p53 alleviated the phenotype of Palb2GT/GT embryos, but did not rescue embryonic lethality. In addition, loss of p53 did not significantly collaborate with Palb2 heterozygosity in tumourigenesis in heterozygous or homozygous p53 knockout mice. Tumours arising in Palb2GT/+;p53+/– or Palb2GT/+;p53–/– compound mutant mice retained the wild type Palb2 allele and did not display increased genomic instability. Comparison of 15 Palb2GT/+;p53-/- and 11 Palb2+/+;p53-/- lymphomas. Spleen/liver DNA of the same animal was used as reference material.
2011-01-21 | E-GEOD-26723 | biostudies-arrayexpress
Project description:Transcriptome analysis was performed on young leaves from 17-day old sesame seedling. The experiment aimed to shed light on the polar regulatory gene network in sesame under KANADI1 loss of function and identify candidate genes underlie the hyponastic leaf phenotype. We compaired between homozygous lines for either SiCD-A allele contains KAN1 (WT) or SiCD-B allele contains kan1 (mutant) on S.indicum LG8.
2022-01-10 | GSE164511 | GEO
Project description:Transcriptional profiling of Drosophila embryos comparing lola mutant 10-12 hour after egg lay (AEL) embryos to age-matched control embryos. Mutants are homozygous lola nulls (allele lola_ORE76).
2011-12-03 | GSE34121 | GEO