{"doi":"10.1101/2023.10.02.560415","title":"MALDI-IM-MS Imaging of Brain Sterols and Lipids in a Mouse Model of Smith-Lemli-Opitz Syndrome","abstract":"Abstract Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by genetic mutations in the DHCR7 gene, which encodes the enzyme 3β-hydroxysterol-Δ 7 -reductase (DHCR7) that catalyzes the last step of cholesterol synthesis, resulting in deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). To understand how the brain regions are differentially affected by the defective Dhcr7, we aim to map the regional distribution of sterols and other lipids in neonatal brains from a Dhcr7 -KO mouse model of SLOS, using mass spectrometry imaging (MSI). MSI enables spatial localization of biomolecules in situ on the surface of a tissue section, which is particularly useful for mapping the changes that occur within a metabolic disorder such as SLOS, and in an anatomically complex organ such as the brain. In this work, using MALDI-ion mobility (IM)-MSI, we successfully determined the regional distribution of features that correspond to cholesterol, 7-DHC/desmosterol, and the precursor of desmosterol, 7-dehydrodesmosterol, in WT and Dhcr7 -KO mice. Interestingly, we also observed m/z values that match the major oxysterol metabolites of 7-DHC (DHCEO and hydroxy-7-DHC), which displayed similar patterns to 7-DHC. We then identified brain lipids using m/z and CCS at the Lipid Species-level and curated a collection of MALDI-IM-MS-derived lipid CCS values. Subsequent statistical analysis of regions-of-interest allowed us to identify differentially expressed lipids between Dhcr7 - KO and WT brains, which could contribute to defects in myelination, neurogenesis, neuroinflammation, and learning and memory in SLOS.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395168,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":334296,"name":"Libin Xu","orcid":"0000-0003-1021-5200","position":1,"is_corresponding":false},{"id":493839,"name":"Amy Li","orcid":"0000-0002-7732-3540","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T01:19:18.686170Z","pmid":"37873113","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}