ArticleMolecular biology of the cell2012
A zebrafish model of PMM2-CDG reveals altered neurogenesis and a substrate-accumulation mechanism for N-linked glycosylation deficiency.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Zebrafish models for congenital disorders of glycosylation (CDG): a systematic review.Orphanet journal of rare diseases · 2025Pooled it
- Glycosylation in premature ovarian insufficiency: from genetic etiology to precision diagnostics.Journal of ovarian research · 2026Review
- Establishing an auxin-inducible GFP nanobody-based acute protein knockdown system to mimic hypomorphic mutations during early medaka embryogenesis.Biology open · 2025Article
- Galactose treatment rescues neuromuscular junction transmission in glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) deficient mice.Human molecular genetics · 2025Article
- Resolving Hexose-Phosphates by LC-MS Leads to New Insights in PGM1-CDG Pathophysiology.ACS omega · 2025Article
- Genotype/Phenotype Relationship: Lessons From 137 Patients With PMM2-CDG.Human mutation · 2024Observational
- Article
- A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation.Development (Cambridge, England) · 2021Article
- A Dominant Heterozygous Mutation inFrontiers in cell and developmental biology · 2021Article
- A Great Catch for Investigating Inborn Errors of Metabolism-Insights Obtained from Zebrafish.Biomolecules · 2020Review
- Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG.Disease models & mechanisms · 2019Article
- Yeast Models of Phosphomannomutase 2 Deficiency, a Congenital Disorder of Glycosylation.G3 (Bethesda, Md.) · 2019Article
- Article
- Mammalian STT3A/B oligosaccharyltransferases segregate N-glycosylation at the translocon from lipid-linked oligosaccharide hydrolysis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- MPDU1 regulates CEACAM1 and cell adhesion in vitro and in vivo.Glycoconjugate journal · 2018Article
- CDG Therapies: From Bench to Bedside.International journal of molecular sciences · 2018Review
- Nrf2 activation attenuates genetic endoplasmic reticulum stress induced by a mutation in the phosphomannomutase 2 gene in zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Article
- DPAGT1-CDG: Functional analysis of disease-causing pathogenic mutations and role of endoplasmic reticulum stress.PloS one · 2017Article
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Authors and funding
11 authors at 4 institutions in 1 country.
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Abstract
Congenital disorder of glycosylation (PMM2-CDG) results from mutations in pmm2, which encodes the phosphomannomutase (Pmm) that converts mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P). Patients have wide-spectrum clinical abnormalities associated with impaired protein N-glycosylation. Although it has been widely proposed that Pmm2 deficiency depletes M1P, a precursor of GDP-mannose, and consequently suppresses lipid-linked oligosaccharide (LLO) levels needed for N-glycosylation, these deficiencies have not been demonstrated in patients or any animal model. Here we report a morpholino-based PMM2-CDG model in zebrafish. Morphant embryos had developmental abnormalities consistent with PMM2-CDG patients, including craniofacial defects and impaired motility associated with altered motor neurogenesis within the spinal cord. Significantly, global N-linked glycosylation and LLO levels were reduced in pmm2 morphants. Although M1P and GDP-mannose were below reliable detection/quantification limits, Pmm2 depletion unexpectedly caused accumulation of M6P, shown earlier to promote LLO cleavage in vitro. In pmm2 morphants, the free glycan by-products of LLO cleavage increased nearly twofold. Suppression of the M6P-synthesizing enzyme mannose phosphate isomerase within the pmm2 background normalized M6P levels and certain aspects of the craniofacial phenotype and abrogated pmm2-dependent LLO cleavage. In summary, we report the first zebrafish model of PMM2-CDG and uncover novel cellular insights not possible with other systems, including an M6P accumulation mechanism for underglycosylation.
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