title: Multimodal detection of GM2 and GM3 lipid species in the brain of mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and immunohistochemistry.
abstract: Mucopolysaccharidosis type II (Hunter's disease) mouse model (IdS-KO) was investigated by both imaging mass spectrometry (IMS) and immunohistochemistry (IHC) performed on the same tissue sections. For this purpose, IdS-KO mice brain sections were coated with sublimated 1,5-diaminonaphtalene and analyzed by high spatial resolution IMS (5 μm) and anti-GM3 IHC on the same tissue sections to characterize the ganglioside monosialated ganglioside (GM) deposits found in Hunter's disease. IMS analysis have found that two species of GM3 and GM2 that are only different due to the length of their fatty acid residue (stearic or arachidic residue) were overexpressed in the IdS-KO mice compared to a control mouse. GM3 and GM2 were characterized by on-tissue exact mass and MS/MS compared to a GM3 standard. Realignment of both IMS and IHC data sets further confirmed the observed regioselective signal previously detected by providing direct correlation of the IMS image for the two GM3 overly expressed MS signals with the anti-GM3 IHC image. Furthermore, these regioselective GM MS signals were also found to have highly heterogeneous distributions within the GM3-IHC staining. Some deposits showed high content in GM3 and GM2 stearic species (r = 0.74) and others had more abundant GM3 and GM2 arachidic species (r = 0.76). Same-section analysis of Hunter's disease mouse model by both high spatial resolution IMS and IHC provides a more in-depth analysis of the composition of the GM aggregates while providing spatial distribution of the observed molecular species. Graphical Abstract Ganglioside imaging mass spectrometry followed by immunohistochemistry performed on the same tissue section.
authors.affiliation: Department of Chemistry, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, QC, H3C 3J7, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Dufresne
authors.affiliation: Department of Chemistry, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, QC, H3C 3J7, Canada.|Département de chimie, Université P. et M. Curie, 4 place Jussieu, 75252, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Guneysu
authors.affiliation: Department of Chemistry, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, QC, H3C 3J7, Canada.
authors.forename: Nathan Heath
authors.initials: NH
authors.lastname: Patterson
authors.affiliation: Cytochem Inc., 6465 Durocher Avenue, Montréal, QC, H2V 3Z1, Canada.
authors.forename: Mieczyslaw Martin
authors.initials: MM
authors.lastname: Marcinkiewicz
authors.affiliation: Angiochem Inc., 201 Avenue du Président-Kennedy, Montréal, QC, H2X 3Y7, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Regina
authors.affiliation: Angiochem Inc., 201 Avenue du Président-Kennedy, Montréal, QC, H2X 3Y7, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Demeule
authors.affiliation: Department of Chemistry, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, QC, H3C 3J7, Canada. pierre.chaurand@umontreal.ca.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chaurand
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005678:G(M2) Ganglioside / Q000378:metabolism*; D005679:G(M3) Ganglioside / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D016532:Mucopolysaccharidosis II / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D005679:G(M3) Ganglioside; D005678:G(M2) Ganglioside
keywords: Ganglioside; Hunter’s disease; Imaging mass spectrometry; Matrix-assisted laser desorption ionization