Mfsd5-KO Mouse

Mfsd5, belonging to the Major Facilitator Superfamily Pfam clan, is a putative solute carrier (SLC) transporter. As an SLC, it may be responsible for the movement of soluble molecules across cellular membranes, potentially playing a role in energy homeostasis [2]. It has a wide central and peripheral mRNA distribution, with abundant protein expression in the mouse embryo and adult mouse brain, expressed in excitatory and inhibitory neurons but not in astrocytes [2].

In the context of valvular heart disease, unbiased ligand-receptor capture mass spectrometry identified Mfsd5 as a novel receptor/cofactor involved in lipoprotein(a) (Lp(a)) uptake. Reducing Mfsd5 expression via a small molecule or small interfering RNA suppressed Lp(a) uptake and calcification in primary human valvular endothelial and interstitial cells. Mfsd5 variants were also associated with aortic stenosis, suggesting a role in cardiovascular diseases [1].

In conclusion, Mfsd5 has potential functions in energy homeostasis as indicated by its expression changes in response to starvation or high-fat diet in mice. Additionally, its role in Lp(a) uptake and association with aortic stenosis in valvular heart disease highlight its importance in cardiovascular research. Studies on Mfsd5 contribute to understanding the underlying mechanisms of energy regulation and cardiovascular diseases, potentially paving the way for new therapeutic strategies.

References:

1. Rogers, Maximillian A, Bartoli-Leonard, Francesca, Zheng, Kang H, Singh, Sasha A, Aikawa, Elena. 2023. Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease. In Circulation, 149, 391-401. doi:10.1161/CIRCULATIONAHA.123.066822. https://pubmed.ncbi.nlm.nih.gov/37937463/

2. Perland, Emelie, Lekholm, Emilia, Eriksson, Mikaela M, Arapi, Vasiliki, Fredriksson, Robert. 2016. The Putative SLC Transporters Mfsd5 and Mfsd11 Are Abundantly Expressed in the Mouse Brain and Have a Potential Role in Energy Homeostasis. In PloS one, 11, e0156912. doi:10.1371/journal.pone.0156912. https://pubmed.ncbi.nlm.nih.gov/27272503/