ArticleBMC developmental biology2008
Transcriptional regulation of mouse alpha A-crystallin gene in a 148kb Cryaa BAC and its derivates.
Article in BMC developmental biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Crystallin gene expression: Insights from studies of transcriptional bursting.Experimental eye research · 2021Review
- Considerations for the use of Cre recombinase for conditional gene deletion in the mouse lens.Human genomics · 2019Article
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- Transcriptional burst fraction and size dynamics during lens fiber cell differentiation and detailed insights into the denucleation process.The Journal of biological chemistry · 2018Article
- Signaling and Gene Regulatory Networks in Mammalian Lens Development.Trends in genetics : TIG · 2017Review
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- Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival.Progress in retinal and eye research · 2016Review
- Regulation of c-Maf and αA-Crystallin in Ocular Lens by Fibroblast Growth Factor Signaling.The Journal of biological chemistry · 2016Article
- Differentiation of Induced Pluripotent Stem Cells to Lentoid Bodies Expressing a Lens Cell-Specific Fluorescent Reporter.PloS one · 2016Article
- Chromatin features, RNA polymerase II and the comparative expression of lens genes encoding crystallins, transcription factors, and autophagy mediators.Molecular vision · 2015Article
- Temporal and spatial changes in VEGF, αA- and αB-crystallin expression in a mouse model of oxygen-induced retinopathy.International journal of clinical and experimental medicine · 2015Article
- Crystallins in retinal ganglion cell survival and regeneration.Molecular neurobiology · 2013Review
- Article
- Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
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4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundalphaA-crystallin is highly expressed in the embryonic, neonatal and adult mouse lens. Previously, we identified two novel distal control regions, DCR1 and DCR3. DCR1 was required for transgenic expression of enhanced green fluorescent protein, EGFP, in lens epithelium, whereas DCR3 was active during "late" stages of lens primary fiber cell differentiation. However, the onset of transgenic EGFP expression was delayed by 12-24 hours, compared to the expression of the endogenous Cryaa gene.
resultsHere, we used bacterial artificial chromosome (BAC) and standard transgenic approaches to examine temporal and spatial regulation of the mouse Cryaa gene. Two BAC transgenes, with EGFP insertions into the third coding exon of Cryaa gene, were created: the intact alphaA-crystallin 148 kb BAC (alphaA-BAC) and alphaA-BAC(DeltaDCR3), which lacks approximately 1.0 kb of genomic DNA including DCR3. Expression of EGFP in the majority of both BAC transgenics nearly recapitulated the endogenous expression pattern of the Cryaa gene in lens, but not outside of the lens. The number of cells expressing alphaA-crystallin in the lens pit was higher compared to the number of cells expressing EGFP. Next, we generated additional lines using a 15 kb fragment of alphaA-crystallin locus derived from alphaA-BAC(DeltaDCR3), 15 kb Cryaa/EGFP. A 15 kb region of Cryaa/EGFP supported the expression pattern of EGFP also in the lens pit. However, co-localization studies of alphaA-crystallin and EGFP indicated that the number of cells that showed transgenic expression was higher compared to cells expressing alphaA-crystallin in the lens pit.
conclusionWe conclude that a 148 kb alphaA-BAC likely contains all of the regulatory regions required for alphaA-crystallin expression in the lens, but not in retina, spleen and thymus. In addition, while the 15 kb Cryaa/EGFP region also supported the expression of EGFP in the lens pit, expression in regions such as the hindbrain, indicate that additional genomic regions may play modulatory functions in regulating extralenticular alphaA-crystallin expression. Finally, deletion of DCR3 in either alphaA-BAC(DeltaDCR3) or Cryaa (15 kb) transgenic mice result in EGFP expression patterns that are consistent with DCR's previously established role as a distal enhancer active in "late" primary lens fiber cells.
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