RESUMO
Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability, is a monogenic neurodevelopmental disorder caused by a loss-of-function mutation of the FMR1 gene. FMR1 is encoding the Fragile X Messenger Ribonucleo Protein (FMRP) an RNA-binding protein that regulates the translation of synaptic proteins. The absence of FMRP expression has many important consequences on synaptic plasticity and function, leading to the FXS clinical phenotype. Over the last decade, a visual neurosensorial phenotype had been described in the FXS patients as well as in the murine model (Fmr1-/ymice), characterized by retinal deficits associated to retinal perception alterations. However, although the transcriptomic profile in the absence of FMRP has been studied in the cerebral part of the central nervous system (CNS), there are no actual data for the retina which is an extension of the CNS. Herein, we investigate the transcriptomic profile of mRNA from whole retinas of Fmr1-/ymice. Interestingly, we found a specific signature of Fmrp absence on retinal mRNA expression with few common genes compared to other brain studies. Gene Ontology on these retinal specific genes demonstrated an enrichment in retinal development genes as well as in synaptic genes. These alterations could be linked to the reported retinal phenotype of the FXS condition. In conclusion, we describe for the first time, retinal-specific transcriptomic changes in the absence of FMRP.
Assuntos
Modelos Animais de Doenças , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil , Retina , Transcriptoma , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Animais , Camundongos , Retina/metabolismo , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Camundongos Endogâmicos C57BL , Perfilação da Expressão Gênica , Camundongos Knockout , Regulação da Expressão Gênica/fisiologia , MasculinoRESUMO
The novel HLA-DPB1*14:01:15 allele differs from DPB1*14:01:01:01 by change of C > T in exon 3.
Assuntos
Alelos , Sequência de Bases , Éxons , Cadeias beta de HLA-DP , Teste de Histocompatibilidade , Doadores de Tecidos , Humanos , Cadeias beta de HLA-DP/genética , Brasil , Análise de Sequência de DNA/métodos , Medula Óssea , Alinhamento de Sequência , Códon , Transplante de Medula ÓsseaRESUMO
HLA-DQB1*02:211 allele differs from DQB1*02:02:01:02 by change of C â A in exon 2.
Assuntos
Alelos , Éxons , Cadeias beta de HLA-DQ , Doadores de Tecidos , Humanos , Cadeias beta de HLA-DQ/genética , Brasil , Teste de Histocompatibilidade , Transplante de Medula Óssea , Sequência de Bases , Análise de Sequência de DNA/métodos , Códon , Medula ÓsseaRESUMO
The new HLA-DRB3*03:69 allele differs from DRB3*03:01:01:03 by change of C â G in exon 3.
Assuntos
Alelos , Éxons , Cadeias HLA-DRB3 , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade , Humanos , Sequência de Bases , Códon , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Teste de Histocompatibilidade/métodos , Cadeias HLA-DRB3/genética , Alinhamento de Sequência , Análise de Sequência de DNA/métodosRESUMO
To prevent ocular pathologies, new generation of dietary supplements have been commercially available. They consist of nutritional supplement mixing components known to provide antioxidative properties, such as unsaturated fatty acid, resveratrol or flavonoids. However, to date, few data evaluating the impact of a mixture mainly composed of those components (Nutrof Total®) on the retina are available. Only one in-vivo preclinical study demonstrated that dietary supplementation (DS) prevents the retina from light-induced retinal degeneration; and only one in-vitro study on Müller cells culture showed that glutamate metabolism cycle was key in oxidative stress response. Therefore, we raised the question about the in-vivo effect of DS on glutamate metabolism in the retina. Herein, we showed that the dietary supplementation promotes in-vivo increase of retinal glutamine amount through a higher glutamine synthesis as observed in-vitro on Muller cells. Therefore, we can suggest that the promotion of glutamine synthesis is part of the protective effect of DS against retinal degeneration, acting as a preconditioning mechanism against retinal degeneration.
Assuntos
Antioxidantes , Suplementos Nutricionais , Ácidos Graxos Ômega-3 , Glutamina , Retina , Degeneração Retiniana , Glutamina/metabolismo , Animais , Antioxidantes/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Degeneração Retiniana/metabolismo , Degeneração Retiniana/prevenção & controle , Retina/metabolismo , Retina/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células Cultivadas , Células Ependimogliais/metabolismo , Células Ependimogliais/efeitos dos fármacos , Masculino , Ratos , Modelos Animais de DoençasRESUMO
The new HLA-DPA1*01:182 allele differs from HLA-DPA1*01:03:01:04 by a single mismatch in exon 4.
Assuntos
Medula Óssea , Cadeias alfa de HLA-DP , Humanos , Alelos , Brasil , Teste de HistocompatibilidadeRESUMO
We identified two new HLA-DRB3 alleles in Brazilian individuals using next generation sequencing.
Assuntos
Medula Óssea , Humanos , Cadeias HLA-DRB3 , Alelos , BrasilRESUMO
HLA-A*68:190:02 differs from A*68:190:01 by a single synonymous nucleotide change in exon 2.
Assuntos
Medula Óssea , Humanos , Alelos , Brasil , Éxons/genéticaRESUMO
Four new HLA-B alleles were identified in Brazilian individuals using next generation sequencing.
