Dataset Information

Morquio A syndrome: identification of differential patterns of molecular pathway interactions in bone lesions

ABSTRACT: Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. The identification of biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone

DISEASE(S): Mucopolysaccharidosis Iva

SUBMITTER: Susana Bravo

LAB HEAD: Susana Belén Bravo López

PROVIDER: PXD042166 | Pride | 2024-05-24

REPOSITORIES: Pride

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Morquio A Syndrome: Identification of Differential Patterns of Molecular Pathway Interactions in Bone Lesions.

Álvarez J Victor JV Bravo Susana B SB Chantada-Vázquez María Pilar MP Pena Carmen C Colón Cristóbal C Tomatsu Shunji S Otero-Espinar Francisco J FJ Couce María L ML

International journal of molecular sciences 20240312 6

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild- ...[more]

PMID: 38542208

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Project description:We used 8 strains the BXD mouse genetic reference population, including parents C57BL/6J and DBA/2J, to study the proteome of the heart, whole brain, liver, quadriceps, and brown adipose tissue (BAT) across 8 different genotypes. For each sample, we examined the proteome of the mitochondria, as well as the whole cell fraction (including mitochondria). Later, we supplemented this study with an additional 19 strains of BXD mouse, with one strain overlapping, in the BAT for both whole cell and mitochondrial extract to examine tissue-specific hypotheses generated from the original set of 8 strains. All together, these data allowed us to (1) examine proteome expression of the mitochondria, (2) examine differences in proteome expression across tissue, (3) examine differences in proteome expression across strain, and (4) examine all three of the preceding factors simultaneously against one-another. This allowed us to uncover several proteins which are expressed in the mitochondria but are not reported as such in the literature, of which we validated a few by traditional staining techniques. Furthermore, we compare our proteome data against transcriptome data gathered in the same individual mice. We observe (1) that differences in expression of genes involved in oxidative phosphorylation are far more tissue-dependent at the protein level than the transcript level, and (2) and we observe that the phenotypic relationship between BAT and thermogenesis is far more evident at the protein expression data than it is from the transcript expression. Together, these data provide two conclusions: (1) next-gen mass spectrometry proteomics techniques can identify organelle localizations that were not evident from other techniques (perhaps particularly those proteins which are expressed both inside and outside the mitochondria); and (2) proteome and transcriptome data are complimentary, and proteome data may help us find and test new hypotheses even for physiological pathways which have been well studied at the genetic and transcriptomic levels.

			Action	DRS
	Bone.sf3	Other
	BoneUNT1DDA.wiff	Wiff
	BoneUNT1DDA.wiff.scan	Wiff
	BoneUNT1SWATH.wiff	Wiff
	BoneUNT1SWATH.wiff.scan	Wiff