Experimental System to Study Instability of (CGG)n Repeats in Cultured Mammalian Cells.

Experimental System to Study Instability of (CGG)n Repeats in Cultured Mammalian Cells. Methods Mol Biol. 2020;2056:137-150 Authors: Kononenko AV, Ebersole T, Mirkin SM Abstract Expansions of simple trinucleotide repeats, such as (CGG)n, (CAG)n or (GAA)n, are responsible for more than 40 hereditary disorders in humans including fragile X syndrome, Huntington's disease, myotonic dystrophy, and Friedreich's ataxia. While the mechanisms of repeat expansions were intensively studied for over two decades, the final picture has yet to emerge. It was important, therefore, to develop a mammalian experimental system for studying repeat instability, which would recapitulate repeat instability observed in human pedigrees. Here, we describe a genetically tractable experimental system to study the instability of (CGG)n repeats in cultured mammalian cells (Kononenko et al., Nat Struct Mol Biol 25:669-676, 2018). It is based on a selectable cassette carrying the HyTK gene under the control of the FMR1 promoter with carrier-size (CGG)n repeats in its 5' UTR, which was integrated into the unique RL5 site in murine erythroid leukemia cells. Expansions of these repeats and/or repeat-induced mutagenesis shut down the reporter, which results in the accumulation of ganciclovir-resistance cells. This system is useful for understanding the genetic controls of repeat instability in mammalian cells. In the long run, it can be adjusted to screen for drugs that either alleviate rep...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research

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In this study, we have used a novel DNAzyme based approach to create a larval model of FXS in zebrafish with specific focus on the early developmental window.MethodsFmr1specific DNAzymes were electroporated into embryos to create theknockdown. Changes in RNA and protein levels of FMRP and relevant biomarkers were measured in the 0-7dpf window. Behavioral tests to measure anxiety, cognitive impairments and irritability in the larvae were conducted at the 7dpf stage. Drug treatment was carried out at various time points in the 0-7dpf window to identify the critical window for pharmacological intervention.ResultsThe DNAzyme b...
Source: Journal of Pharmacological and Toxicological Methods - Category: Drugs & Pharmacology Source Type: research
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Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
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Source: Drugs of Today - Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research
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Source: Cadernos de Saude Publica - Category: International Medicine & Public Health Authors: Tags: Cad Saude Publica Source Type: research
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Source: Journal of Hematopathology - Category: Pathology Source Type: research
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