Tmem86b-KO Mouse

Tmem86b, an integral membrane protein of the YhhN family, functions as a lysoplasmalogenase [1,2,3]. It catalyzes the hydrolytic cleavage of the vinyl-ether bond of lysoplasmalogen, yielding fatty aldehyde and glycerophospho-ethanolamine or glycerophospho-choline, and is thus involved in plasmalogen catabolism [1,2,3]. Understanding its role can be crucial for studying lipid metabolism-related biological processes. Genetic models, such as gene knockout mouse models, are valuable tools to explore its function in vivo.

In a study generating global and hepatocyte-specific Tmem86b knockout mice, homozygous global inactivation of Tmem86b led to significantly elevated levels of plasmalogens (alkenylphosphatidylethanolamine, alkenylphosphatidylcholine) and lysoplasmalogens in the plasma, liver, and natural killer cells. Hepatocyte-specific knockout mice also showed increased plasmalogen levels in the plasma and liver. This indicates that Tmem86b plays a key role in regulating plasmalogen levels in these tissues and cells [4].

In conclusion, Tmem86b is an important lysoplasmalogenase involved in plasmalogen catabolism. The Tmem86b knockout mouse models have revealed its role in maintaining proper plasmalogen levels in certain tissues, which may be relevant to understanding lipid-related disorders and potentially developing therapeutic strategies targeting plasmalogen metabolism [4].

References:

1. Jurkowitz, Marianne S, Patel, Aalapi, Wu, Lai-Chu, Pfeiffer, Douglas R, Bell, Charles E. 2014. The YhhN protein of Legionella pneumophila is a Lysoplasmalogenase. In Biochimica et biophysica acta, 1848, 742-51. doi:10.1016/j.bbamem.2014.11.011. https://pubmed.ncbi.nlm.nih.gov/25445671/

2. Kummer, Denise, Dorigatti, Ilaria, Dunzendorfer-Matt, Theresia, Werner, Ernst R, Watschinger, Katrin. 2025. Functional characterization of TMEM86A and TMEM86B mutants by a novel lysoplasmalogenase assay. In Journal of lipid research, 66, 100766. doi:10.1016/j.jlr.2025.100766. https://pubmed.ncbi.nlm.nih.gov/40024572/

3. Wu, Lai-Chu, Pfeiffer, Douglas R, Calhoon, Elisabeth A, Liu, Shujun, Jurkowitz, Marianne S. 2011. Purification, identification, and cloning of lysoplasmalogenase, the enzyme that catalyzes hydrolysis of the vinyl ether bond of lysoplasmalogen. In The Journal of biological chemistry, 286, 24916-30. doi:10.1074/jbc.M111.247163. https://pubmed.ncbi.nlm.nih.gov/21515882/

4. Paul, Sudip, Morgan, Pooranee, Pernes, Gerard, Lancaster, Graeme I, Meikle, Peter J. 2025. Modulation of endogenous plasmalogens by genetic ablation of lysoplasmalogenase (Tmem86b) in mice. In Journal of lipid research, , 100808. doi:10.1016/j.jlr.2025.100808. https://pubmed.ncbi.nlm.nih.gov/40245986/