PUBLICATION
Zebrafish as outgroup model to study evolution of scavenger receptor class B type I functions
- Authors
- Verwilligen, R.A.F., Mulder, L., Araújo, P.M., Carneiro, M., Bussmann, J., Hoekstra, M., Van Eck, M.
- ID
- ZDB-PUB-230318-42
- Date
- 2023
- Source
- Biochimica et biophysica acta. Molecular and cell biology of lipids 1868(6): 159308 (Journal)
- Registered Authors
- Bussmann, Jeroen
- Keywords
- Cholesterol metabolism, Evolution, Fertility, Scavenger receptor, Scavenger receptor class B type I
- MeSH Terms
-
- Animals
- Cholesterol*
- Cholesterol, HDL
- Female
- Mammals
- Scavenger Receptors, Class B/genetics
- Zebrafish*/genetics
- PubMed
- 36931457 Full text @ BBA Molecular and Cell Biology of Lipids
Citation
Verwilligen, R.A.F., Mulder, L., Araújo, P.M., Carneiro, M., Bussmann, J., Hoekstra, M., Van Eck, M. (2023) Zebrafish as outgroup model to study evolution of scavenger receptor class B type I functions. Biochimica et biophysica acta. Molecular and cell biology of lipids. 1868(6):159308.
Abstract
Background and aims Scavenger receptor class B1 (SCARB1) - also known as the high-density lipoprotein (HDL) receptor - is a multi-ligand scavenger receptor that is primarily expressed in liver and steroidogenic organs. This receptor is known for its function in reverse cholesterol transport (RCT) in mammals and hence disruption leads to a massive increase in HDL cholesterol in these species. The extracellular domain of SCARB1 - which is important for cholesterol handling - is highly conserved across multiple vertebrates, except in zebrafish.
Methods To examine the functional conservation of SCARB1 among vertebrates, two stable scarb1 knockout zebrafish lines, scarb1 715delA (scarb1 -1 nt) and scarb1 715_716insGG (scarb1 +2 nt), were created using CRISPR-Cas9 technology.
Results We demonstrate that, in zebrafish, SCARB1 deficiency leads to disruption of carotenoid-based pigmentation, reduced fertility, and a decreased larvae survival rate, whereas steroidogenesis was unaltered. The observed reduced fertility is driven by defects in female fertility (-50 %, p < 0.001). Importantly, these alterations were independent of changes in free (wild-type 2.4 ± 0.2 μg/μl versus scarb1-/- 2.0 ± 0.1 μg/μl) as well as total (wild-type 4.2 ± 0.4 μg/μl versus scarb1-/- 4.0 ± 0.3 μg/μl) plasma cholesterol levels. Uptake of HDL in the liver of scarb1-/- zebrafish larvae was reduced (-86.7 %, p < 0.001), but this coincided with reduced perfusion of the liver. No effect was observed on lipoprotein uptake in the caudal vein. SCARB1 deficient canaries, which also lack carotenoids in their plumage, similarly as scarb1-/- zebrafish, failed to show an increase in plasma free- and total cholesterol levels.
Conclusion Our findings suggest that the specific function of SCARB1 in maintaining plasma cholesterol could be an evolutionary novelty that became prominent in mammals, while other known functions were already present earlier during vertebrate evolution.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping