eprintid: 21404
rev_number: 12
eprint_status: archive
userid: 2588
dir: disk0/00/02/14/04
datestamp: 2016-07-01 07:54:21
lastmod: 2016-07-22 11:14:57
status_changed: 2016-07-01 07:54:21
type: doctoralThesis
metadata_visibility: show
creators_name: Benz, Alexander
title: miR-19b - ein essentieller Regulator der Länge und Form
des ventrikulären Aktionspotentials im Zebrafisch
divisions: i-140001
adv_faculty: af-14
abstract: Sudden cardiac death (SCD) is a common mode of death in heart failure (HF) and results
from prolonged action potential duration (APD) and ventricular arrhythmias. During the
pathogenesis and progression of HF, a myriad number of signaling pathways are altered,
including microRNAs. microRNAs are small noncoding RNAs that fine-tune gene expression
by translational repression or transcript destabilization. Interestingly, microRNAs are
dysregulated during HF, suggesting a potential involvement in the development and
progression of the disease. Here, miR-19 was identified as an important regulator of heart
function. Zebrafish lacking miR-19 developed severe bradycardia and reduced cardiac
contractility. While mammals express two isoforms of miR-19, the zebrafish genome encodes
for four members (19a-d). The reduction of miR-19b specifically was found to be sufficient to
reduce heart rate by 30 % and to induce heart failure. Patch-clamp experiments from whole
hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular
APD caused by impaired repolarization. Additionally these fish show increased sensitivity to
an AV-Block, which is a characteristic feature of long QT-Syndrome in zebrafish. qRT-PCR
revealed that miR-19b directly and indirectly regulates the expression of cardiac ion channels
and thereby modulates APD and shape. This study describes miR-19b as an essential
regulator of electrical activity of the heart and identifies it as a potential candidate gene
causative for human long QT syndrome.
date: 2016
id_scheme: DOI
id_number: 10.11588/heidok.00021404
ppn_swb: 1657872351
own_urn: urn:nbn:de:bsz:16-heidok-214043
date_accepted: 2016-06-03
advisor: HASH(0x55fc36bba6e0)
language: ger
bibsort: BENZALEXANMIR19BEINE2016
full_text_status: public
citation:   Benz, Alexander  (2016) miR-19b - ein essentieller Regulator der Länge und Form des ventrikulären Aktionspotentials im Zebrafisch.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/21404/1/20160404%20Alexander%20Benz%20Dissertation.pdf