Transcriptome profiling from Wild Type and Lss mutant (heterozygous and homozygous) lens at E14.5 reveals the potential pathways involved in cataract formation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE185143 | GEO | 2021/12/23
REPOSITORIES: GEO
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Project description:The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-third of these rats develop lens opacity within 10-11-weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR is poorly understood. Our study aimed to identify the gene expression patterns during cataract formation in SCRs, which may be responsible for cataractogenesis in SCR.
2020-07-31 | GSE152616 | GEO
Project description:Although majority of the genes linked to pediatric cataract exhibit lens fiber cell-enriched expression, our understanding of gene regulation in these cells is limited to function of just eight transcription factors and largely in the context of crystallins. Here, we identify small Maf transcription factors MafG and MafK as regulators of several non-crystallin human cataract genes in fiber cells and establish their significance to cataract. We applied a bioinformatics tool for cataract gene discovery iSyTE to identify MafG and its co-regulators in the lens, and generated various null-allelic combinations of MafG:MafK mouse mutants for phenotypic and molecular analysis. By age 4-months, MafG-/-:MafK+/- mutants exhibit lens defects that progressively develop into cataract. High-resolution phenotypic characterization of MafG-/-:MafK+/- lens reveals severe defects in fiber cells, while microarrays-based expression profiling identifies 97 differentially regulated genes (DRGs). Integrative analysis of MafG-/-:MafK+/- lens-DRGs with 1) binding-motifs and genomic targets of small Mafs and their regulatory partners, 2) iSyTE lens-expression data, and 3) interactions between DRGs in the String database, unravels a detailed small Maf regulatory network in the lens, several nodes of which are linked to human cataract. This analysis prioritizes 36 highly promising candidates from the original 97 DRGs. Significantly, 8/36 (22%) DRGs are associated with cataracts in human (GSTO1, MGST1, SC4MOL, UCHL1) or mouse (Aldh3a1, Crygf, Hspb1, Pcbd1), suggesting a multifactorial etiology that includes elevation of oxidative stress. These data identify MafG and MafK as new cataract-associated candidates and define their function in regulating largely non-crystallin genes linked to mouse and human cataract. Microarray comparision of lenses from mixed background (129Sv/J, C57BL/6J, and ICR) control (MafG+/-:MafK+/-; no-cataract) and compound (MafG-/-:MafK+/-; cataract) mouse mutants
2015-05-01 | E-GEOD-65500 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from Tdrd7 knockdown cells compared to lentiviral GFP control in 21EM15 lens epithelial-derived cell line
2012-02-21 | E-GEOD-25774 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from P30 Lens from Tdrd7 null mice compared to that of Tdrd7 heterozygous mice.
2012-02-21 | E-GEOD-25776 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from P4 Lens from Tdrd7 null mice compared to that of Tdrd7 heterozygous mice.
2012-02-21 | E-GEOD-25775 | biostudies-arrayexpress
Project description:Although majority of the genes linked to pediatric cataract exhibit lens fiber cell-enriched expression, our understanding of gene regulation in these cells is limited to function of just eight transcription factors and largely in the context of crystallins. Here, we identify small Maf transcription factors MafG and MafK as regulators of several non-crystallin human cataract genes in fiber cells and establish their significance to cataract. We applied a bioinformatics tool for cataract gene discovery iSyTE to identify MafG and its co-regulators in the lens, and generated various null-allelic combinations of MafG:MafK mouse mutants for phenotypic and molecular analysis. By age 4-months, MafG-/-:MafK+/- mutants exhibit lens defects that progressively develop into cataract. High-resolution phenotypic characterization of MafG-/-:MafK+/- lens reveals severe defects in fiber cells, while microarrays-based expression profiling identifies 97 differentially regulated genes (DRGs). Integrative analysis of MafG-/-:MafK+/- lens-DRGs with 1) binding-motifs and genomic targets of small Mafs and their regulatory partners, 2) iSyTE lens-expression data, and 3) interactions between DRGs in the String database, unravels a detailed small Maf regulatory network in the lens, several nodes of which are linked to human cataract. This analysis prioritizes 36 highly promising candidates from the original 97 DRGs. Significantly, 8/36 (22%) DRGs are associated with cataracts in human (GSTO1, MGST1, SC4MOL, UCHL1) or mouse (Aldh3a1, Crygf, Hspb1, Pcbd1), suggesting a multifactorial etiology that includes elevation of oxidative stress. These data identify MafG and MafK as new cataract-associated candidates and define their function in regulating largely non-crystallin genes linked to mouse and human cataract.
2015-05-01 | GSE65500 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25776 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25775 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25774 | GEO
Project description:We investigated the therapeutic effects of histone acetyltransferase (HAT) inhibitors on cataracts using an ex vivo model of galactose-induced cataracts in the rat lens.Among the tested HAT inhibitors, TH1834 was the only inhibitor that could completely reverse white opacities once formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. To identify the genes regulated by HAT inhibitors, we conducted microarray analysis of treated and untreated cataract samples.
2022-12-11 | GSE186248 | GEO