Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Retinas from the Pex1-G844D mouse model of Zellweger spectrum disorder

ABSTRACT: Gene expression analysis of retinas from a mouse model of the mild form of Zellweger spectrum disorder (ZSD). Mice homozygous for the hypomorphic Pex1-G844D allele, the murine ortholog of the human PEX1-G843D mutation found in a subset of patients with autosomal recessive ZSD, develop phenotypes found in humans with a milder form of ZSD, including retinal degeneration and vision loss. Similar to humans, mice heterozygous for the hypomorphic Pex1-G844D allele do not display age-related retinal abnormalities. We conducted a comparative analysis of retinal gene expression profile from Pex1-G844D homozygous and heterozygous mice in order to investigate the pathomechanisms of vision loss in humans with mild forms of ZSD.

ORGANISM(S): Mus musculus

PROVIDER: GSE52348 | GEO | 2013/12/15

SECONDARY ACCESSION(S): PRJNA227465

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Retinas from the Pex1-G844D mouse model of Zellweger spectrum disorder

Project description:Gene expression analysis of retinas from a mouse model of the mild form of Zellweger spectrum disorder (ZSD). Mice homozygous for the hypomorphic Pex1-G844D allele, the murine ortholog of the human PEX1-G843D mutation found in a subset of patients with autosomal recessive ZSD, develop phenotypes found in humans with a milder form of ZSD, including retinal degeneration and vision loss. Similar to humans, mice heterozygous for the hypomorphic Pex1-G844D allele do not display age-related retinal abnormalities. We conducted a comparative analysis of retinal gene expression profile from Pex1-G844D homozygous and heterozygous mice in order to investigate the pathomechanisms of vision loss in humans with mild forms of ZSD. Whole retinas were obtained from 4 mice homozygous and 4 mice heterozygous for the hypomorphic Pex1-G844D allele, the murine ortholog of the human PEX1-G843D mutation found in a subset of patients with autosomal recessive Zellweger spectrum disorder (ZSD). The former group of animals show abnormal age-related related retinal degeneration due to peroxisome assembly defect resulting from having two copies of the hypomorphic Pex1-G844D allele. The latter group of animals display no evidence of abnormal age-related retinal degeneration due to the presence of one wild type copy of the Pex1 gene. The overall goal was to identify differentially expressed genes between mice homozygous and heterozygous for the hypomorphic Pex1-G844D allele that are informative of the pathomechanisms of age-related retinal degeneration in the former group.

2013-12-15 | E-GEOD-52348 | biostudies-arrayexpress

Pex1-G844D NMRI mouse model of mild Zellweger spectrum disorder: liver gene expression profiles

Project description:Zellweger spectrum disorders (ZSD) are inborn metabolic diseases cause by genetic alterations in PEX genes leading to peroxisomal biogenesis disorder (PBD). Supportive care is standard since no validated treatment is able to modify the dismal natural history of the disease. Mouse models exist to study ZSD pathophysiology but they are limited by poor survival of the affected pups and breeding restrictions. To overcome these limitations, hypomorphic Pex1 p.G844D allele, equivalent to common mild human PEX1 p.G843D mutation, was backcrossed from C57BL/6N mouse to NMRI background. NMRI ZSD mouse breeding lead autosomal recessive Mendelian inheritance pattern with (median (min-max)) 10 (7-15) pups/mating compared to 4 (2-7) pups/mating in C57BL/6N background (p < 0.0001). We longitudinally phenotyped NMRI ZSD mice at 1, 2, 3 and 6 months of age to render this model suitable for future therapeutic interventions. NMRI ZSD mice exhibited growth retardation despite their higher daily energy intake. Mouse embryonic fibroblasts displayed classical PBD immunofluorescence pattern with peroxisomal mosaicism like milder ZSD patients skin fibroblasts. ZSD mice liver were enlarged and no liver lipid accumulation was detected. Yet, ZSD mouse plasma and liver showed very long-chain fatty acids, oxysterols and C27 bile acids intermediates elevation. Longitudinal study depicted trend to normalization for C26 and phytanic acid as it was shown for some ZSD patients reaching adulthood. ZSD mouse liver glycogen content was drastically reduced and liver RNA-Seq analysis confirmed glycogen metabolism genes downregulation. In conclusion, NMRI ZSD mouse model is suitable for ZSD liver-targeted therapies evaluation.

2020-02-20 | GSE145524 | GEO

A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 mutant mice III

Project description:These datasets contain the transcriptomes from E12.5 mouse retinal tissues from embryos carrying three different combinations of the Vsx2 ocular retardation J (orJ) allele and the Mitf mi (mi) allele: orJ-heterozygous, which serves as the control, orJ-homozygous, and orJ-homozygous; mi-heterozygous. The orJ allele is a recessive loss of function and the mi allele is semi-dominant. Mitf is direct target of repression by Vsx2 in the retina and is an established causal factor in the orJ ocular phenotype of microphthalmia. The goal of this analysis was to determine if blocking Mitf function in the orJ mutant would restore retinal gene expression to wild type levels. All libraries were prepared and sequenced together, facilitating direct comparisons of the gene expression profiles across the 3 genotypes.

2023-05-19 | GSE227055 | GEO

A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 mutant mice

Project description:This SuperSeries is composed of the SubSeries listed below. The Vsx2 homeobox gene is expressed in the newly formed retinal domain during early eye development and mutations in the Vsx2 gene cause congenital microphthalmia. The primary disruptions in the early retina are compromised retinal identity (lineage infidelity), reduced proliferation, and delayed neurogenesis. One goal of the study was to use gene expression profiling to predict genetic interactions between Vsx2 and candidate functional interactors that contribute to the early retinal phenotype of the Vsx2-null mouse strain ocular retardation J (orJ). The orJ allele is a spontaneous, recessive allele caused by the presence of a premature stop codon in the Vsx2 homeodomain. The datasets contained within are from three independent experimental designs. One was to compare the retinal gene expression profiles from E12.5 embryos that are one of three genotypes: the orJ-homozygous mutant, the combinatorial orJ; Mitfmi heterozygous mutant, and the orJ-heterozygous mouse (control). Another analysis was to compare the gene expression profiles of E12.5 orJ-homozygous mutant retinal tissues cultured for 24 hour in the presence or absence of the RXR antagonist HX531. The other analysis was to compare the gene expression profiles of E12.5 orJ-homozygous mutant retinal tissues cultured for 24 hour in the presence or absence of the gamma-Secretase antagonist Dibenzazipine (DBZ).

2023-05-19 | GSE227056 | GEO

A genotype directed dose-finding study of Irinotecan (CPT-11) by groups of Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphisms in patients with advanced metastatic colorectal cancer and gastric cancer.

Project description:Interventions: Administraion of CPT-11 is twice for 4 weeks on days 1 and 15. CPT-11 is reconstituted in >=250 mL of normal saline or 5% dextrose in water and infuse 90min on day 1 for pharmacokinetics, and 90min over on day15. CPT-11 adjusted dosage is determined from 50,75,100,125 or 150mg/sqm in the heterozygous group and the homozygous group by continual reassessment method. CPT-11 dosage is fixed at 150mg/sqm in the wild group.Definision of UGT1A1 polymorphisms groups: The homozygous group is patient with homozygous genotype of UGT1A1*28/*28 or UGT1A1*6/*6, with combined heterozygous genotypes of UGT1A1*28 and UGT1A1*6. The heterozygous group is patient with heterozygous genotype of either UGT1A1*28 or UGT1A1*6. The wild group is patients with no UGT1A1*28 and UGT1A1*6 mutation. Primary outcome(s): Maximum tolerated dose for the heterozygous group and the homozygous group, respectively. Incidence rate of dose limiting toxicities for the wild group. Study Design: Single arm Non-randomized

| 2616019 | ecrin-mdr-crc

A feasibility study of Irinotecan (CPT-11) by groups of Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphisms in patients with metastatic colorectal cancer.

Project description:Interventions: Patients receive FOLFIRI with bevacizumab fixed 5mg/kg. (Treatment will be continued unless the disease progression, unacceptable toxicity, or consent withdrawal.) Definision of UGT1A1 polymorphisms groups: The homozygous group is patient with homozygous genotype of UGT1A1*28/*28 or UGT1A1*6/*6, with combined heterozygous genotypes of UGT1A1*28 and UGT1A1*6. The heterozygous group is patient with heterozygous genotype of either UGT1A1*28 or UGT1A1*6. The wild group is patients with no UGT1A1*28 and UGT1A1*6 mutation. CPT-11 dosage is wild and heterozygous:CPT-11 150mg/m2 homozygous:CPT-11 100mg/m2 Primary outcome(s): 1)incidence of adverse events 2)frequency of severe toxicity Study Design: Single arm Non-randomized

| 2620216 | ecrin-mdr-crc

Personalized use of irinotecan in colorectal cancer patients based on real world studies and pharmacogenomics

Project description:Interventions: Wild-type group:None;Single heterozygous group:None;Mutant homozygous/double heterozygous group:None Primary outcome(s): Efficacy;The incidence of adverse events Study Design: Cohort study

| 89703 | ecrin-mdr-crc

Gene expression changes in mouse hematopoietic stem cell enriched populations following the loss of Meis1 expression

Project description:Hematopoietic stem cell enriched Lin-Sca1+cKit+ cells were isolated from heterozygous and homozygous transgenic mice with a loxP-flanked Meis1 allele following in vivo allele deletion.

2016-02-04 | E-MTAB-4133 | biostudies-arrayexpress

FACS-array profiling in retinal endothelial cells from living mouse retinas

Project description:Deregulated retinal angiogenesis directly cause vision loss in many ocular diseases, such as diabetic retinopathy and retinopathy of prematurity. To identify endothelial-specific genes expressed in angiogenic retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice and performed gene expression profiling using DNA microarray. To find out genes associated with angiogenesis, comparisons of microarray data were carried out between GFP-negative non-endothelial retinal cells and GFP-positive retinal endothelial cells in angiogenic P8 retina. Eighteen arrays are included. Utilizing fluorescence-activated cell sorting (FACS), we isolated endothelial cells as GFP-positive cells from P8 retina in homozygous Tie2-GFP transgenic mice. GFP-negative cells were served as non-endothelial control. RNA extracts from sorted cells were amplified and then hybridized to Affymetrix MGU74v2 series arrays in triplicate.

2011-04-17 | E-GEOD-27238 | biostudies-arrayexpress

Expression in the dorsal telencephalon of E13.5 conditional Dicer KO mice

Project description:To study the effect of miRNA depletion in the embryonic forebrain, we isolated RNA from E13.5 dorsal telencephalon of mice homozygous for a floxed Dicer allele and hemizygous for the forebrain expressed Emx1Cre (Dicer KO mice). These samples were compared to littermates heterozygous for the floxed allele and hemizygous for Emx1Cre.

2012-08-30 | GSE37610 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data