Correction: Tagger-A Swiss army knife for multiomics to dissect cell type-specific mechanisms of gene expression in mice.

[This corrects the article DOI: 10.1371/journal.pbio.3000374.].

Tagger-A Swiss army knife for multiomics to dissect cell type-specific mechanisms of gene expression in mice.

A deep understanding of how regulation of the multiple levels of gene expression in mammalian tissues give rise to complex phenotypes has been impeded by cellular diversity. A handful of techniques were developed to tag-select nucleic acids of interest in specific cell types, thereby enabling their capture. We expanded this strategy by developing the Tagger knock-in mouse line bearing a quad-cistronic transgene combining enrichment tools for nuclei, nascent RNA, translating mRNA, and mature microRNA (miRNA). We demonstrate that Tagger can capture the desired nucleic acids, enabling multiple omics approaches to be applied to specific cell types in vivo using a single transgenic mouse line.

Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice.

PURPOSE: Desmin mutations in humans cause desmin-related cardiomyopathy, resulting in heart failure, atrial and ventricular arrhythmias, and sudden cardiac death. The intermediate filament desmin is strongly expressed in striated muscle cells and in Purkinje fibers of the ventricular conduction system. The aim of the present study was to characterize electrophysiological cardiac properties in a desmin-deficient mouse model. METHODS: The impact of desmin deficiency on cardiac electrophysiological characteristics was examined in the present study. In vivo electrophysiological studies were carried out in 29 adult desmin deficient (Des-/-) and 19 wild-type (Des+/+) mice. Additionally, epicardial activation mapping was performed in Langendorff-perfused hearts. RESULTS: Intracardiac electrograms showed no significant differences in AV, AH, and HV intervals. Functional testing revealed equal AV-nodal refractory periods, sinus-node recovery times, and Wenckebach points. However, compared to the wild-type situation, Des-/- mice were found to have a significantly reduced atrial (23.6+/-10.3 ms vs. 31.8+/-12.5 ms; p=0.045), but prolonged ventricular refractory period (33.0+/-8.7 ms vs. 26.7+/-6.5 ms; p=0.009). The probability of induction of atrial fibrillation was significantly higher in Des-/- mice (Des-/-: 38% vs. Des+/+: 27%; p=0.0255), while ventricular tachycardias significantly were reduced (Des-/-: 7% vs. Des+/+: 21%; p<0.0001). Epicardial activation mapping showed slowing of conduction in the ventricles of Des-/- mice. CONCLUSIONS: Des-/- mice exhibit reduced atrial but prolonged ventricular refractory periods and ventricular conduction slowing, accompanied by enhanced inducibility of atrial fibrillation and diminished susceptibility to ventricular arrhythmias. Desmin deficiency does not result in electrophysiological changes present in human desminopathies, suggesting that functional alterations rather than loss of desmin cause the cardiac alterations in these patients.