Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

Durrant, Andrea R.; Tamayev, Liliya; Anglister, Lili

doi:10.3389/fnmol.2012.00073

Cited by 13 publications

(12 citation statements)

References 52 publications

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“…In addition, a higher diversity in body weight was characteristic of the mutant mice. Similar dynamics have been shown for mdx mice, as they were shown to gain body weight comparably to wild-type mice by 11 weeks of age (Durrant et al, 2012).…”

Section: Discussionsupporting

confidence: 72%

CRISPR/Cas9-generated mouse model of Duchenne muscular dystrophy recapitulating a newly identified large 430 kb deletion in the human DMD gene

Егорова

Zotova²,

Reshetov

et al. 2019

Disease Models &Amp; Mechanisms

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Exon skipping is a promising strategy for Duchenne muscular dystrophy (DMD) disease-modifying therapy. To make this approach safe, ensuring that excluding one or more exons will restore the reading frame and that the resulting protein will retain critical functions of the full-length dystrophin protein is necessary. However, in vivo testing of the consequences of skipping exons that encode the N-terminal actin-binding domain (ABD) has been confounded by the absence of a relevant animal model. We created a mouse model of the disease recapitulating a novel human mutation, a large de novo deletion of exons 8-34 of the DMD gene, found in a Russian DMD patient. This mutation was achieved by deleting exons 8-34 of the X-linked mouse D md gene using CRISPR/Cas9 genome editing, which led to a reading frame shift and the absence of functional dystrophin production. Male mice carrying this deletion display several important signs of muscular dystrophy, including a gradual age-dependent decrease in muscle strength, increased creatine kinase, muscle fibrosis and central nucleation. The degrees of these changes are comparable to those observed in mdx mice, a standard laboratory model of DMD. This new model of DMD will be useful for validating therapies based on skipping exons that encode the N-terminal ABD and for improving our understanding of the role of the N-terminal domain and central rod domain in the biological function of dystrophin. Simultaneous skipping of exons 6 and 7 should restore the gene reading frame and lead to the production of a protein that might retain functionality despite the partial deletion of the ABD.

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Section: Discussionsupporting

confidence: 72%

CRISPR/Cas9-generated mouse model of Duchenne muscular dystrophy recapitulating a newly identified large 430 kb deletion in the human DMD gene

Егорова

Zotova²,

Reshetov

et al. 2019

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…This difference in performance indicated the necessity to investigate each of the different batches and lots separately when using polyclonal antibodies. While an interaction and functional relationship between BCHE and IGF1 was previously hypothesized 39,40 , the concordant enrichment data from two different antibodies suggests that both proteins may likely be bound another in plasma.…”

Section: Resultsmentioning

confidence: 69%

Systematic assessment of antibody selectivity in plasma based on a resource of enrichment profiles

Fredolini

Byström

Sánchez-Rivera

et al. 2019

Sci Rep

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There is a strong need for procedures that enable context and application dependent validation of antibodies. Here, we applied a magnetic bead assisted workflow and immunoprecipitation mass spectrometry (IP-MS/MS) to assess antibody selectivity for the detection of proteins in human plasma. A resource was built on 414 IP experiments using 157 antibodies (targeting 120 unique proteins) in assays with heat-treated or untreated EDTA plasma. For each protein we determined their antibody related degrees of enrichment using z-scores and their frequencies of identification across all IP assays. Out of 1,313 unique endogenous proteins, 426 proteins (33%) were detected in >20% of IPs, and these background components were mainly comprised of proteins from the complement system. For 45% (70/157) of the tested antibodies, the expected target proteins were enriched (z-score ≥ 3). Among these 70 antibodies, 59 (84%) co-enriched other proteins beside the intended target and mainly due to sequence homology or protein abundance. We also detected protein interactions in plasma, and for IGFBP2 confirmed these using several antibodies and sandwich immunoassays. The protein enrichment data with plasma provide a very useful and yet lacking resource for the assessment of antibody selectivity. Our insights will contribute to a more informed use of affinity reagents for plasma proteomics assays.

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“…Based on substrate and inhibitor specificity cholinesterases are classified as Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) [10]. AChE, true ChE, is found in red blood cells, while BChE, pseudocholinesterase, is found in plasma or serum [11]. Natural and synthetically produced inhibitors of enzyme AChE activity are used for disease treatment [12].…”

Section: Introductionmentioning

confidence: 99%

Effect of water intake and storage time on protein concentration and enzyme AChE activity in erythrocyte and plasma blood samples of healthy individuals

Jovičić

2020

Preprint

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Background: Storage time influence concentration levels of blood biomarker. This study aimed to assess the effect of water intake prior sampling and storage time on protein concentration, enzyme AChE activity, inhibitor efficacy and to build an efficient inhibitor calibration curve in healthy individuals. Methods: Data analysis was performed on 11 participants. Study utilizes substrate acetylcholine chloride and inhibitors BW284c51 (0.01mM) and GUK-987 (0.1mM). Calibration curve ranging from 10-1 to 10-38 mM was build for inhibitor GUK-987 and GDK-510. Data analysis is carried out with Microsoft Excel 2007. Data analysis was performed via IBM SPSS Statistical Software v23.0. Descriptive statistics and parametric statistical tests were assessed for 0, 90, 91 and 92 days of storage in Plasma and Erythrocyte samples. Workflow of building calibration curve and the most efficient inhibition concentration is assessed. Results: Water intake and storage time have effect on in vitro protein concentration, activation/inhibition of enzyme AChE activity in Plasma and Erythrocyte samples. However, 100% inhibitor efficacy is maintained for inhibitor GUK-987 in Plasma samples and inhibitor BW284c51 in Erythrocyte samples. The most efficient inhibitor concentration is determined. Conclution: Significant changes and variable association have been estimated between protein concentration, activation/inhibition of enzyme AChE activity, as a cause of water intake and storage time. Taking all these factors into account for further research is important for disease prevention and human wellbeing. Keywords: Water intake, Storage time, Enzyme AChE, Erythrocyte samples, Plasma sample, Healthy individuals

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Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

Cited by 13 publications

References 52 publications

CRISPR/Cas9-generated mouse model of Duchenne muscular dystrophy recapitulating a newly identified large 430 kb deletion in the human DMD gene

CRISPR/Cas9-generated mouse model of Duchenne muscular dystrophy recapitulating a newly identified large 430 kb deletion in the human DMD gene

Systematic assessment of antibody selectivity in plasma based on a resource of enrichment profiles

Effect of water intake and storage time on protein concentration and enzyme AChE activity in erythrocyte and plasma blood samples of healthy individuals

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