Mutations in pank2 gene encoding pantothenate kinase 2 determine a pantothenate kinase-associated neurodegeneration, a rare disorder characterized by iron deposition in the globus pallidus. To extend our previous work, we performed microinjections of a new pank2-specific morpholino to zebrafish embryos and thoroughly analyzed vasculature development. Vessels development was severely perturbed in the head, trunk, and tail, where blood accumulation was remarkable and associated with dilation of the posterior cardinal vein. This phenotype was specific as confirmed by p53 expression analysis and injection of the same morpholino in pank2-mutant embryos. We can conclude that pank2 gene is involved in vasculature development in zebrafish embryos. The comprehension of the underlining mechanisms could be of relevance for understanding of pantothenate kinase-associated neurodegeneration.
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Di Meo I, Carecchio M, Tiranti V. Inborn Errors of Coenzyme A Metabolism and Neurodegeneration. J. Inherit. Metab. Dis. 2019;42(1):49-56. https://doi.org/10.1002/jimd.12026
Gagnon JA, Valen E, Thyme SB, Huang P, Akhmetova L, Pauli A, Montague TG, Zimmerman S, Richter C, Schier AF. Efficient Mutagenesis by Cas9 Protein-Mediated Oligonucleotide Insertion and Large-Scale Assessment of Single-Guide RNAs. PLoS One. 2014;9(5):e98186. https://doi.org/10.1371/journal.pone.0098186
Gatta LB, Vitali M, Verardi R, Arosio P, Finazzi D. Inhibition of heme synthesis alters Amyloid Precursor Protein processing. J. Neural. Transm. (Vienna). 2009;116(1):79-88. https://doi.org/10.1007/s00702-008-0147-z
Gregory A, Polster BJ, Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J. Med. Genet. 2009;46(2):73-80. https://doi.org/10.1136/jmg.2008.061929
Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, Gitschier J. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N. Engl. J. Med. 2003;348(1):33-40. https://doi.org/10.1056/NEJMoa020817
Khatri D, Zizioli D, Tiso N, Facchinello N, Vezzoli S, Gianoncelli A, Memo M, Monti E, Borsani G, Finazzi D. Down-regulation of Coasy, the Gene Associated With NBIA-VI, Reduces Bmp Signaling, Perturbs Dorso-Ventral Patterning and Alters Neuronal Development in Zebrafish. Sci. Rep. 2016;6:37660. https://doi.org/10.1038/srep37660
Khatri D, Zizioli D, Trivedi A, Borsani G, Monti E, Finazzi D. Overexpression of Human Mutant PANK2 Proteins Affects Development and Motor Behavior of Zebrafish Embryos. Neuromolecular Med. 2019;21(2):120-131. https://doi.org/10.1007/s12017-018-8508-8
Lambrechts RA, Schepers H, Yu Y, van der Zwaag M, Autio KJ, Vieira-Lara MA, Bakker BM, Tijssen MA, Hayflick SJ, Grzeschik NA, Sibon OC. CoA-dependent Activation of Mitochondrial Acyl Carrier Protein Links Four Neurodegenerative Diseases. EMBO Mol. Med. 2019;11(12):e10488. https://doi.org/10.15252/emmm.201910488
Levi S, Finazzi D. Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms. Front. Pharmacol. 2014;5:99. https://doi.org/10.3389/fphar.2014.00099
Pagani F, Trivedi A, Khatri D, Zizioli D, Garrafa E, Mitola S, Finazzi D. Silencing of Pantothenate Kinase 2 Reduces Endothelial Cell Angiogenesis. Mol. Med. Rep. 2018;18(5):4739-4746. https://doi.org/10.3892/mmr.2018.9480
Siudeja K, Srinivasan B, Xu L, Rana A, de Jong J, Nollen EA, Jackowski S, Sanford L, Hayflick S, Sibon OC. Impaired Coenzyme A Metabolism Affects Histone and Tubulin Acetylation in Drosophila and Human Cell Models of Pantothenate Kinase Associated Neurodegeneration. EMBO Mol. Med. 2011;3(12):755-766. https://doi.org/10.1002/emmm.201100180
Srinivasan B, Baratashvili M, van der Zwaag M, Kanon B, Colombelli C, Lambrechts RA, Schaap O, Nollen EA, Podgoršek A, Kosec G, Petković H, Hayflick S, Tiranti V, Reijngoud DJ, Grzeschik NA, Sibon OC. Extracellular 4’-phosphopantetheine Is a Source for Intracellular Coenzyme A Synthesis. Nat. Chem. Biol. 2015;11(10):784-92. https://doi.org/10.1038/nchembio.1906
Stainier DYR, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS, Ingham PW, Schulte-Merker S, Yelon D, Weinstein BM, Mullins MC, Wilson SW, Ramakrishnan L, Amacher SL, Neuhauss SCF, Meng A, Mochizuki N, Panula P, Moens CB. Guidelines for morpholino use in zebrafish. PLoS Genet. 2017;13(10):e1007000. https://doi.org/10.1371/journal.pgen.1007000
Zizioli D, Tiso N, Guglielmi A, Saraceno C, Busolin G, Giuliani R, Khatri D, Monti E, Borsani G, Argenton F, Finazzi D. Knock-down of Pantothenate Kinase 2 Severely Affects the Development of the Nervous and Vascular System in Zebrafish, Providing New Insights Into PKAN Disease. Neurobiol. Dis. 2016;85:35-48. https://doi.org/10.1016/j.nbd.2015.10.010
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 7, pp. 72-78, July, 2020
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Khatri, D., Mignani, L., Zizioli, D. et al. Abnormal Vasculature Development in Zebrafish Embryos with Reduced Expression of Pantothenate Kinase 2 Gene. Bull Exp Biol Med 170, 58–63 (2020). https://doi.org/10.1007/s10517-020-05004-3
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DOI: https://doi.org/10.1007/s10517-020-05004-3