Brain transcriptome profile after CRISPR-induced ghrelin mutations in zebrafish



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Blanco, Ayelén Melisa and Cortés, Raul and Bertucci, Juan Ignacio and Soletto, Lucía and Sánchez, Elisa and Valenciano, Ana Isabel and Cerdá-Reverter, José Miguel and Delgado, María Jesús (2019) Brain transcriptome profile after CRISPR-induced ghrelin mutations in zebrafish. Fish Physiology and Biochemistry, 46 . pp. 1-21. ISSN 1573-5168

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Ghrelin (GRL) is a gut-brain hormone with a role in a wide variety of physiological functions in mammals and fish, which points out the ghrelinergic system as a key element for the appropriate biological functioning of the organism. However, many aspects of the multifunctional nature of GRL remain to be better explored, especially in fish. In this study, we used the CRISPR/Cas9 genome editing technique to generate F0 zebrafish in which the expression of grl is compromised. Then, we employed high-throughput mRNA sequencing (RNA-seq) to explore changes in the brain transcriptome landscape associated with the silencing of grl. The CRISPR/Cas9 technique successfully edited the genome of F0 zebrafish resulting in individuals with considerably lower levels of GRL mRNAs and protein and ghrelin O-acyl transferase (goat) mRNAs in the brain, intestine, and liver compared to wild-type (WT) zebrafish. Analysis of brain transcriptome revealed a total of 1360 differentially expressed genes (DEGs) between the grl knockdown (KD) and WT zebrafish, with 664 up- and 696 downregulated DEGs in the KD group. Functional enrichment analysis revealed that DEGs are highly enriched for terms related to morphogenesis, metabolism (especially of lipids), entrainment of circadian clocks, oxygen transport, apoptosis, and response to stimulus. The present study offers valuable information on the central genes and pathways implicated in functions of GRL, and points out the possible involvement of this peptide in some novel functions in fish, such as apoptosis and oxygen transport.

Item Type:Article
Uncontrolled Keywords:Ghrelinergic system, CRISPR/Cas9, knockdown, RNA-seq, transcriptomic, fish
Subjects:Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Genetics
Medical sciences > Biology > Fishes
ID Code:61425
Deposited On:09 Jul 2020 10:22
Last Modified:09 Jul 2020 10:22

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