Tmem86a-flox Mouse

TMEM86A, also known as transmembrane protein 86A, is a putative lysoplasmalogenase. Lysoplasmalogens are key in plasmalogen metabolism and membrane fluidity. TMEM86A is involved in regulating plasmalogen homeostasis and is associated with protein kinase A-dependent energy metabolism pathways. Its study using genetic models can help understand its role in various biological processes and diseases [1,2].

In adipocyte-specific TMEM86A-knockout (AKO) mice, lysoplasmalogen content in adipose tissue increases, accompanied by an elevation in protein kinase A signalling pathways due to phosphodiesterase 3B inhibition and cyclic adenosine monophosphate elevation. This leads to upregulated mitochondrial oxidative metabolism, increased energy expenditure, and protection from high-fat diet-induced metabolic dysfunction [1].

In macrophages, TMEM86a (a related form) is a sterol-regulated lysoplasmalogenase. Overexpression in bone marrow-derived macrophages (BMDMs) reduces lysoplasmalogen abundance and membrane fluidity, while silencing increases basal lysoplasmalogen levels and abolishes liver X receptor (LXR)-dependent reduction of this lipid species [2].

In conclusion, TMEM86A is crucial for regulating plasmalogen homeostasis and energy metabolism. Studies using KO mouse models have revealed its potential as a therapeutic target for obesity-related metabolic diseases. In macrophages, it contributes to sterol-dependent membrane remodeling. Understanding TMEM86A provides insights into lipid metabolism and related disease mechanisms [1,2].