Mlec-KO Mouse

MLEC, also known as Malectin, is a membrane-anchored endoplasmic reticulum (ER)-resident lectin. It plays a crucial role in the quality control of glycoprotein in the ER by recognizing the Glc2Man9GlcNAc2 (G2M9) oligosaccharide chain on newly synthesized glycoproteins [4].

In the context of diseases, MLEC gene polymorphisms have been associated with cerebral palsy (CP). Specific single nucleotide polymorphisms (SNPs) of MLEC, such as rs10431386 and rs7964786, were found to be significantly associated with the risk of CP in the Chinese Han population. The C alleles of these SNPs inhibit MLEC expression in the blood of CP patients and macrophage cell lines. In vitro experiments showed that MLEC promotes M1 to M2 macrophage polarization, and the C alleles on MLEC promote CP by inhibiting this polarization [1]. Additionally, MLEC has been identified as a potential characteristic marker for papillary thyroid carcinoma (PTC) as proteomic profiling detected its overexpression in PTC compared to normal surrounding tissues [2]. Recent research also indicates that MLEC promotes coronavirus replication and viral protein biogenesis. Knocking down MLEC significantly reduces infectious titers, and during infection, MLEC-associated proteins interact with viral non-structural proteins, and its interactome is altered to stabilize association with the Oligosaccheryltransferase (OST) complex, crucial for viral glycoprotein production [3].

In conclusion, MLEC is essential for glycoprotein quality control in the ER. Studies on MLEC gene polymorphisms and its role in macrophage polarization have provided insights into the pathogenesis of CP. Its potential as a marker for PTC and its role in coronavirus replication further highlight its significance in disease-related research. These findings contribute to a better understanding of disease mechanisms and may offer new directions for diagnosis and treatment in relevant disease areas.

References:

1. Shi, W, Zhu, Y, Zhou, M, Chen, X, Chen, X. 2018. Malectin gene polymorphisms promote cerebral palsy via M2-like macrophage polarization. In Clinical genetics, 93, 794-799. doi:10.1111/cge.13149. https://pubmed.ncbi.nlm.nih.gov/28972276/

2. Ban, Yoshiyuki, Yamamoto, Gou, Takada, Michiya, Tachikawa, Tetsuhiko, Hirano, Tsutomu. 2012. Proteomic profiling of thyroid papillary carcinoma. In Journal of thyroid research, 2012, 815079. doi:10.1155/2012/815079. https://pubmed.ncbi.nlm.nih.gov/22518348/

3. Davies, Jonathan P, Plate, Lars. 2024. The glycoprotein quality control factor Malectin promotes coronavirus replication and viral protein biogenesis. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.06.02.597051. https://pubmed.ncbi.nlm.nih.gov/38895409/

4. Qin, Sheng-Ying, Hu, Dan, Yamamoto, Kazuo. . Preparation of Soluble Malectin and Its Tetramer. In Methods in molecular biology (Clifton, N.J.), 2132, 285-294. doi:10.1007/978-1-0716-0430-4_28. https://pubmed.ncbi.nlm.nih.gov/32306336/