PXD078307

PXD078307 is an original dataset announced via ProteomeXchange.

Title	Asialoglycoprotein receptor subunit ASGR1a deficiency leads to cholesterol malabsorption in zebrafish on a high cholesterol diet
Description	One of the major pathways to clear glycoproteins from circulation is via the liver-specific asialoglycoprotein receptor (ASGPR). Recently, loss of asialoglycoprotein receptor 1 (ASGR1), the major subunit of ASGPR in humans, was found to correlate with lower levels of plasma apolipoprotein B-containing lipoproteins (B-lps) and a profound reduction in cardiovascular disease risk. However, the cell and molecular biology underlying this effect was unclear. Given that rodents carry their cholesterol largely in HDL, we selected the zebrafish model to better understand the mechanism(s) of action of ASGR1. We first characterized all possible zebrafish ASGR1 orthologs to identify zebrafish ASGR1 (asgr1a) from a collection of lectin-binding proteins. We then generated two independent mutations in asgr1a using CRISPR/Cas9. Neither mutation altered larval, juvenile, or adult B-lp numbers or sizes. However, when challenged with a Western diet, asgr1a mutant zebrafish exhibited less hepatic steatosis and lower hepatic triglyceride levels compared to control animals. Asgr1a mutant animals also exhibited increased levels of fecal cholesterol, which we found was due to malabsorption after a meal, and upregulation of liver proteins known to be involved in B-lp metabolism (e.g. MTP, APOA4). These data are consistent with the atheroprotective role of ASGR1 and reveal a previously unappreciated role for ASGR1 in modulating whole animal cholesterol flux.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_04:21:46.283.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joshua Derrick
SpeciesList	scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: NEWT:7955;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-13 19:48:36	ID requested
⏵ 1	2026-09-07 04:21:47	announced

10.1016/j.jbc.2026.113239;

Derrick JT, Moll TOC, Sweeney DW, Shin J, Svecla M, Norata GD, Farber SA, Asialoglycoprotein receptor subunit Asgr1a loss results in attenuated cholesterol absorption in zebrafish fed a western diet. J Biol Chem, 302(8):113239(2026) [pubmed]

submitter keyword: ASGR1, steatosis, cholesterol,Liver, Zebrafish

Steve Farber
contact affiliation	Johns Hopkins University Baltimore, MD 21218 USA
contact email	sfarber3@jh.edu
lab head
Joshua Derrick
contact affiliation	Johns Hopkins University
contact email	jderric4@jh.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/09/PXD078307

PRIDE project URI

• PRIDE
  1. PXD078307
     1. Label: PRIDE project
     2. Name: Asialoglycoprotein receptor subunit ASGR1a deficiency leads to cholesterol malabsorption in zebrafish on a high cholesterol diet