Probing the changes in gene expression due to α-crystallin mutations in mouse models of hereditary human cataract
| العنوان: | Probing the changes in gene expression due to α-crystallin mutations in mouse models of hereditary human cataract |
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| المؤلفون: | Usha P. Andley, Eric Tycksen, Paul D. Hamilton, Brittney N. McGlasson-Naumann |
| المصدر: | PLoS ONE, Vol 13, Iss 1, p e0190817 (2018) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteomics, Molecular biology, Mutant, Alpha-Crystallin A Chain, Gene Expression, Carboxypeptidases, medicine.disease_cause, Molecular biology assays and analysis techniques, Biochemistry, Histones, Mice, Gene expression, Medicine and Health Sciences, Gene Knock-In Techniques, Lens (Anatomy), Mutation, Multidisciplinary, biology, Nucleic acid analysis, Animal Models, RNA analysis, Cell biology, Histone, Experimental Organism Systems, Medicine, Anatomy, Research Article, Ocular Anatomy, Science, Mice, Transgenic, Mouse Models, alpha-Crystallin A Chain, Cataract, 03 medical and health sciences, Model Organisms, CLIC5, Crystallin, Chloride Channels, Ocular System, Lens, Crystalline, DNA-binding proteins, medicine, Genetics, Animals, Humans, Hemoglobin, Gene, 030102 biochemistry & molecular biology, Biology and life sciences, Cataracts, Proteins, alpha-Crystallin B Chain, Mice, Mutant Strains, eye diseases, Mice, Inbred C57BL, Repressor Proteins, Research and analysis methods, Disease Models, Animal, Ophthalmology, 030104 developmental biology, Molecular biology techniques, Lens Disorders, biology.protein, sense organs |
| الوصف: | The mammalian eye lens expresses a high concentration of crystallins (α, β and γ-crystallins) to maintain the refractive index essential for lens transparency. Crystallins are long-lived proteins that do not turnover throughout life. The structural destabilization of crystallins by UV exposure, glycation, oxidative stress and mutations in crystallin genes leads to protein aggregation and development of cataracts. Several destabilizing mutations in crystallin genes are linked with human autosomal dominant hereditary cataracts. To investigate the mechanism by which the α-crystallin mutations Cryaa-R49C and Cryab-R120G lead to cataract formation, we determined whether these mutations cause an altered expression of specific transcripts in the lens at an early postnatal age by RNA-seq analysis. Using knock-in mouse models previously generated in our laboratory, in the present work, we identified genes that exhibited altered abundance in the mutant lenses, including decreased transcripts for Clic5, an intracellular water channel in Cryaa-R49C heterozygous mutant lenses, and increased transcripts for Eno1b in Cryab-R120G heterozygous mutant lenses. In addition, RNA-seq analysis revealed increased histones H2B, H2A, and H4 gene expression in Cryaa-R49C mutant lenses, suggesting that the αA-crystallin mutation regulates histone expression via a transcriptional mechanism. Additionally, these studies confirmed the increased expression of histones H2B, H2A, and H4 by proteomic analysis of Cryaa-R49C knock-in and Cryaa;Cryab gene knockout lenses reported previously. Taken together, these findings offer additional insight into the early transcriptional changes caused by Cryaa and Cryab mutations associated with autosomal dominant human cataracts, and indicate that the transcript levels of certain genes are affected by the expression of mutant α-crystallin in vivo. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::684b66230d955fa6c582f16032abbeb8Test https://doaj.org/article/5fab3fb3577a4ec7b1ec4b52d0640cddTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....684b66230d955fa6c582f16032abbeb8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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