Man2b1-KO Mouse

MAN2B1, or Mannosidase alpha class 2B member 1, is a lysosomal hydrolase from the α -mannosidase family. It is crucial for the ordered degradation of N -linked glycoproteins through glycan hydrolysis, a process vital for protein function in biological processes [1,3]. Aberrations in MAN2B1 are linked to lysosomal storage disorders, immune interactions, congenital disorders, and tumour progression [1].

Mutations in MAN2B1 lead to α -mannosidosis, an autosomal recessive lysosomal storage disorder. Affected individuals show cognitive impairment, hearing loss, immune system and skeletal anomalies [1,5]. In a Doberman Pinscher dog with a homozygous missense variant in MAN2B1, it presented with neurodegeneration, cytoplasmic vacuoles, and α -mannosidase deficiency [4]. In glioma, MAN2B1 was elevated, correlated with malignant features, and was prognostic for poor outcomes. It was also involved in immune and inflammation processes, and associated with M2 macrophages [3]. In Parkinson's disease, proteome profiling of cerebrospinal fluid identified MAN2B1 as being altered or significantly correlated with clinical scores [2].

In conclusion, MAN2B1 is essential for the degradation of N -linked glycoproteins, and its dysfunction is associated with multiple diseases. Studies in animal models and human disease contexts, such as α -mannosidosis, glioma, and Parkinson's disease, have revealed its role in neurodegeneration, immune-related processes, and as a potential biomarker, highlighting its significance in understanding disease mechanisms and potential therapeutic targeting.

References:

1. Han, Yuwen, Zhou, Yuanshuai, Pan, Jinlin, Sun, Minxuan, Yang, Jiao. 2024. MAN2B1 in immune system-related diseases, neurodegenerative disorders and cancers: functions beyond α-mannosidosis. In Expert reviews in molecular medicine, 27, e4. doi:10.1017/erm.2024.34. https://pubmed.ncbi.nlm.nih.gov/39628046/

2. Karayel, Ozge, Virreira Winter, Sebastian, Padmanabhan, Shalini, Scherzer, Clemens R, Mann, Matthias. . Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease. In Cell reports. Medicine, 3, 100661. doi:10.1016/j.xcrm.2022.100661. https://pubmed.ncbi.nlm.nih.gov/35732154/

3. Lin, Xuelei, Liu, Hongwei, Zhao, Hongyu, Wanggou, Siyi, Li, Xuejun. 2022. Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. In Frontiers in oncology, 12, 842973. doi:10.3389/fonc.2022.842973. https://pubmed.ncbi.nlm.nih.gov/35186771/

4. Bullock, Garrett, Johnson, Gary S, Pattridge, Savannah G, Vite, Charles H, Katz, Martin L. 2023. A Homozygous MAN2B1 Missense Mutation in a Doberman Pinscher Dog with Neurodegeneration, Cytoplasmic Vacuoles, Autofluorescent Storage Granules, and an α-Mannosidase Deficiency. In Genes, 14, . doi:10.3390/genes14091746. https://pubmed.ncbi.nlm.nih.gov/37761886/

5. Malm, Dag, Nilssen, Øivind. 2008. Alpha-mannosidosis. In Orphanet journal of rare diseases, 3, 21. doi:10.1186/1750-1172-3-21. https://pubmed.ncbi.nlm.nih.gov/18651971/