Partial fads2 Gene Knockout Diverts LC-PUFA Biosynthesis via an Alternative Delta 8 Pathway with an Impact on the Reproduction of Female Zebrafish (Danio rerio)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12520%2F22%3A43904466" target="_blank" >RIV/60076658:12520/22:43904466 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.3390/genes13040700" target="_blank" >https://doi.org/10.3390/genes13040700</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/genes13040700" target="_blank" >10.3390/genes13040700</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Partial fads2 Gene Knockout Diverts LC-PUFA Biosynthesis via an Alternative Delta 8 Pathway with an Impact on the Reproduction of Female Zebrafish (Danio rerio)

Popis výsledku v původním jazyce

The zebrafish (Danio rerio) genome contains a single gene fads2 encoding a desaturase (FADS2) with both Delta 6 and Delta 5 activities, the key player in the endogenous biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), which serve essential functions as membrane components, sources of energy and signaling molecules. LC-PUFAs include the precursors of eicosanoids and are thus predicted to be indispensable molecules for reproductive health in virtually all vertebrates. In mice, an amniotic vertebrate, fads2 deletion mutants, both males and females, have been confirmed to be sterile. In anamniotic vertebrates, such as fish, there is still no information available on the reproductive (in)ability of fads2 mutants, although zebrafish have become an increasingly important model of lipid metabolism, including some aspects of the generation of germ cells and early embryonic development. In the present study, we apply the CRISPR/Cas9 genome editing system to induce mutations in the zebrafish genome and create crispants displaying a degree of fads2 gene editing within the range of 50-80%. Focusing on adult G(0) crispant females, we investigated the LC-PUFA profiles of eggs. Our data suggest an impaired pathway of the LC-PUFA biosynthesis of the omega 6 and omega 3 series in the first-rate limiting steps of the conversion of linoleic acid (LA) into gamma-linolenic acid (GLA), and alpha-linolenic acid (ALA) into stearidonic acid (SDA), respectively, finally resulting in bad-quality eggs. Our data suggest the existence of an alternative Delta 8 pathway, which bypasses the first endogenous LC-PUFA biosynthetic step in zebrafish in vivo, and suggest that the zebrafish bifunctional FADS2 enzyme is actually a trifunctional Delta 6/Delta 5/Delta 8 desaturase.

Název v anglickém jazyce

Partial fads2 Gene Knockout Diverts LC-PUFA Biosynthesis via an Alternative Delta 8 Pathway with an Impact on the Reproduction of Female Zebrafish (Danio rerio)

Popis výsledku anglicky

The zebrafish (Danio rerio) genome contains a single gene fads2 encoding a desaturase (FADS2) with both Delta 6 and Delta 5 activities, the key player in the endogenous biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), which serve essential functions as membrane components, sources of energy and signaling molecules. LC-PUFAs include the precursors of eicosanoids and are thus predicted to be indispensable molecules for reproductive health in virtually all vertebrates. In mice, an amniotic vertebrate, fads2 deletion mutants, both males and females, have been confirmed to be sterile. In anamniotic vertebrates, such as fish, there is still no information available on the reproductive (in)ability of fads2 mutants, although zebrafish have become an increasingly important model of lipid metabolism, including some aspects of the generation of germ cells and early embryonic development. In the present study, we apply the CRISPR/Cas9 genome editing system to induce mutations in the zebrafish genome and create crispants displaying a degree of fads2 gene editing within the range of 50-80%. Focusing on adult G(0) crispant females, we investigated the LC-PUFA profiles of eggs. Our data suggest an impaired pathway of the LC-PUFA biosynthesis of the omega 6 and omega 3 series in the first-rate limiting steps of the conversion of linoleic acid (LA) into gamma-linolenic acid (GLA), and alpha-linolenic acid (ALA) into stearidonic acid (SDA), respectively, finally resulting in bad-quality eggs. Our data suggest the existence of an alternative Delta 8 pathway, which bypasses the first endogenous LC-PUFA biosynthetic step in zebrafish in vivo, and suggest that the zebrafish bifunctional FADS2 enzyme is actually a trifunctional Delta 6/Delta 5/Delta 8 desaturase.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Genes

ISSN

2073-4425

e-ISSN

2073-4425

Svazek periodika

13

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

13

Strana od-do

nestrankovano

Kód UT WoS článku

000785468900001

EID výsledku v databázi Scopus

2-s2.0-85125652749