Abnormal Vasculature Development in Zebrafish Embryos with Reduced Expression of Pantothenate Kinase 2 Gene
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Bulletin of Experimental Biology and Medicine, Vol. 170, No. 1, November, 2020
GENETICS Abnormal Vasculature Development in Zebrafish Embryos with Reduced Expression of Pantothenate Kinase 2 Gene
D. Khatri1, L. Mignani1, D. Zizioli1, M. Ritelli2, E. Monti1, and D. Finazzi1 Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 7, pp. 72-78, July, 2020 Original article submitted May 17, 2020 Mutations in pank2 gene encoding pantothenate kinase 2 determine a pantothenate kinaseassociated 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. Key Words: PANK2; zebrafish; coenzyme A; vasculature development
Pantothenate kinase-associated neurodegeneration (PKAN), a rare autosomal recessive disorder characterized by the presence of iron deposits in the globus pallidus [5], is associated with mutations in pank2 gene that encodes for the enzyme catalyzing the first step in coenzyme A (CoA) biosynthesis. It accounts for about 50% cases of neurodegeneration with brain iron accumulation disorders and can present with early onset, rapid progression and prevalence of extrapyramidal symptoms or with later onset, slower progression, parkinsonism, psychiatric and cognitive symptoms [4]. It is not clear yet, whether functional defects in PANK2 gene affect cellular CoA level [1,9]. Recent work suggests that defects in CoA homeostasis could lead to reduced 4’-phosphopantethenylation of mitochondrial acyl carrier protein and hence changes Section of Biotechnology, 2Section of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Address for correspondence: [email protected]. D. Zizioli
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in lipoylation of several proteins, including pyruvate dehydrogenase [8]. Further studies are necessary to understand the biochemical and molecular pathways leading to PKAN. We recently contributed to this challenge by studying pank2 in zebrafish embryos [6,14]. In zebrafish, pank2 is mainly expressed in the CNS and in the vasculature. Knocking down pank2 expression by a specific morpholino led to perturbations of the neuronal development and vasculature formation. We found impaired angiogenesis in mutant embryos with PANK2 overexpression [7] and with downregulation of the coasy gene [6], and also in mammalian cells with PANK2 sile
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