The ORMDL3 asthma susceptibility gene regulates systemic ceramide levels without altering key asthma features in mice.

ABSTRACT:

Background

Genome-wide association studies in asthma have repeatedly identified single nucleotide polymorphisms in the ORM (yeast)-like protein isoform 3 (ORMDL3) gene across different populations. Although the ORM homologues in yeast are well-known inhibitors of sphingolipid synthesis, it is still unclear whether and how mammalian ORMDL3 regulates sphingolipid metabolism and whether altered sphingolipid synthesis would be causally related to asthma risk.

Objective

We sought to examine the in vivo role of ORMDL3 in sphingolipid metabolism and allergic asthma.

Methods

Ormdl3-LacZ reporter mice, gene-deficient Ormdl3^-/- mice, and overexpressing Ormdl3^Tg/wt mice were exposed to physiologically relevant aeroallergens, such as house dust mite (HDM) or

SUBMITTER: Debeuf N 

PROVIDER: S-EPMC7610749 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature