Poster Presentation 29th Annual Lorne Proteomics Symposium 2024

Exploring the Allen Brain Atlas for Mouse Brain Glycomics (#170)

Edward SX Moh 1 2 3 , Sagar Dalal 1 3 , Mark R Hutchinson 4 , Nicolle H Packer 1 2 3
  1. ARC Centre of Nanoscale BioPhotonics, Macquarie University, Sydney, NSW, Australia
  2. ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, NSW, Australia
  3. School Of Natural Sciences, Macquarie University, Sydney, NSW, Australia
  4. ARC Centre of Excellence for Nanoscale Biophotonics, Adelaide, SA, Australia

The Allen Institute Mouse Brain Atlas describes brain region-specific gene expression data using in-situ hybridisation results for more than 20,000 mouse genes [1]. Combined with the visualisation software, Brain Explorer 2.0, this completely open access dataset can be viewed in a 3-dimensional view and overlaid with specific brain regions of interest. Importantly, the gene expression data is normalised such that expression levels of different genes in different brain regions can be directly compared.

In this work, we focused on the region-specific expression of genes related to protein glycosylation [2].  From the existing mouse brain N-glycomics data, it is reported that mouse brain N-glycoproteins are predominantly oligomannosylated, have a high abundance of bisecting GlcNAc glycans, and have no NeuGc, despite being the predominant sialic acid in mouse plasma [3-5]. Based on the knowledge of N-glycan processing pathways, oligomannosylation and bisecting GlcNAc can be correlated with the activity of 2 enzymes, MGAT1 and MGAT3. MGAT1 gatekeeps the transformation of an oligomannose into a hybrid/complex glycan, and MGAT3 adds the bisecting GlcNAc. Similarly, NeuGc levels can be correlated with the levels of the CMAH enzyme that synthesizes CMP-NeuGc. Visual display of the expression of these three genes by the Atlas agrees completely with the currently reported brain N-glycomics datasets. Building upon these correlation examples, we explored the database for previously unknown potential region-specific presence of particular glycan features.

 

  1. Lein, E.S., et al., Genome-wide atlas of gene expression in the adult mouse brain. Nature, 2007. 445(7124): p. 168-176.
  2. Moh, E.S.X., et al., Mouse brain glycomics – Insights from exploring the Allen Brain Atlas and the implications for the neuroimmune brain. Brain, Behavior, and Immunity, 2023. 113: p. 83-90.
  3. Barboza, M., et al., Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis. Mol Cell Proteomics, 2021. 20: p. 100130.
  4. Williams, S.E., et al., Mammalian brain glycoproteins exhibit diminished glycan complexity compared to other tissues. Nature Communications, 2022. 13(1): p. 275.
  5. Lee, J., et al., Spatial and temporal diversity of glycome expression in mammalian brain. Proceedings of the National Academy of Sciences, 2020. 117(46): p. 28743-28753.