Knockout of zebrafish desmin genes does not cause skeletal muscle degeneration but alters calcium flux

TY - JOUR

T1 - Knockout of zebrafish desmin genes does not cause skeletal muscle degeneration but alters calcium flux

AU - Kayman Kürekçi, Gülsüm

AU - Kural Mangit, Ecem

AU - Koyunlar, Cansu

AU - Unsal, Seyda

AU - Saglam, Berk

AU - Ergin, Bora

AU - Gizer, Merve

AU - Uyanik, Ismail

AU - Boustanabadimaralan Düz, Niloufar

AU - Korkusuz, Petek

AU - Talim, Beril

AU - Purali, Nuhan

AU - Hughes, Simon M

AU - Dincer, Pervin R

N1 - Funding Information: This work was supported by The Scientific and Technological Research Council of Turkey, Project No. 214S174 to P.R.D. S.M.H. is an MRC Scientist with MRC Programme Grant G1001029 and MR/N021231/1 support. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4/5

Y1 - 2021/4/5

N2 - Desmin is a muscle-specific intermediate filament protein that has fundamental role in muscle structure and force transmission. Whereas human desmin protein is encoded by a single gene, two desmin paralogs (desma and desmb) exist in zebrafish. Desma and desmb show differential spatiotemporal expression during zebrafish embryonic and larval development, being similarly expressed in skeletal muscle until hatching, after which expression of desmb shifts to gut smooth muscle. We generated knockout (KO) mutant lines carrying loss-of-function mutations for each gene by using CRISPR/Cas9. Mutants are viable and fertile, and lack obvious skeletal muscle, heart or intestinal defects. In contrast to morphants, knockout of each gene did not cause any overt muscular phenotype, but did alter calcium flux in myofibres. These results point to a possible compensation mechanism in these mutant lines generated by targeting nonsense mutations to the first coding exon.

AB - Desmin is a muscle-specific intermediate filament protein that has fundamental role in muscle structure and force transmission. Whereas human desmin protein is encoded by a single gene, two desmin paralogs (desma and desmb) exist in zebrafish. Desma and desmb show differential spatiotemporal expression during zebrafish embryonic and larval development, being similarly expressed in skeletal muscle until hatching, after which expression of desmb shifts to gut smooth muscle. We generated knockout (KO) mutant lines carrying loss-of-function mutations for each gene by using CRISPR/Cas9. Mutants are viable and fertile, and lack obvious skeletal muscle, heart or intestinal defects. In contrast to morphants, knockout of each gene did not cause any overt muscular phenotype, but did alter calcium flux in myofibres. These results point to a possible compensation mechanism in these mutant lines generated by targeting nonsense mutations to the first coding exon.

UR - http://www.scopus.com/inward/record.url?scp=85103997239&partnerID=8YFLogxK

U2 - 10.1038/s41598-021-86974-w

DO - 10.1038/s41598-021-86974-w

M3 - Article

C2 - 33820917

SN - 2045-2322

VL - 11

SP - 7505

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 7505

ER -