Wfs1‐deficient animals have brain‐region‐specific changes of Na+, K+‐ATPase activity and mRNA expression of α1 and β1 subunits

Sütt, Silva; Altpere, Alina; Reimets, Riin; Visnapuu, Tanel; Loomets, Maarja; Raud, Sirli; Salum, Tiit; Mahlapuu, Riina; Kairane, Česlava; Zilmer, Mihkel; Vasar, Eero

doi:10.1002/jnr.23508

Cited by 11 publications

(11 citation statements)

References 42 publications

(50 reference statements)

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“…In the ER, the C-terminal domain of WFS1, which is situated in the ER lumen, interacts with the C-terminal domain (aa 652-890) of Na+/K+ ATPase beta-1 subunit (ATP1B1). Thus, alterations of WFS1 could cause a decrease in Na-pump activity (28).…”

Section: Molecular Biology Physiology and Pathophysiology Of Ws1mentioning

confidence: 99%

Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease

et al. 2018

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Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and other abnormalities. WS1 usually results in death before the age of 50 years. The pathogenesis of WS1 is ascribed to mutations of human WFS1 gene on chromosome 4p encoding a transmembrane protein called wolframin which has physiological functions in membrane trafficking, secretion, processing, and/or regulation of ER calcium homeostasis. Different types of WFS1 mutations have been identified, and some of these have been associated with a dominant, severe type of WS.

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Section: Molecular Biology Physiology and Pathophysiology Of Ws1mentioning

confidence: 99%

Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease

et al. 2018

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“…48 Other highly enriched genes included MCHR1, an important neuroendocrine modulator of appetite that has previously been shown to be associated with schizophrenia, 52 as well as WFS1, associated with Wolfram syndrome, which affects central nervous system development. 53 Our results have to be seen in the light of the following additional limitations. First, our BBT sample was only of moderate size, although larger than previous studies.…”

Section: Discussionmentioning

confidence: 88%

Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research

Walton¹,

Hass

Liu

et al. 2015

SCHBUL

237

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Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders.

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“…WFS1 , located on human chromosome 4p16.1, is composed of eight exons, of which only the first exon is a noncoding exon, and most mutations in WFS1 have been identified in exon 8 but also in exons 3, 4, 5 and 6 6 7 8 . WFS1 encodes the protein wolframin, which is abundantly expressed in pancreas, brain, heart, and muscle and is thought to be a novel endoplasmic reticulum (ER) calcium channel or a regulator of channel activity 9 10 . Additionally, wolframin appears to be involved in membrane trafficking, protein processing 11 , regulation of intracellular Ca 2+ homeostasis 12 and β-cell dysfunction 13 14 .…”

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confidence: 99%

Phenotype Prediction of Pathogenic Nonsynonymous Single Nucleotide Polymorphisms in WFS1

Qian

Qin

Xing

et al. 2015

Sci Rep

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Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder that has an autosomal recessive pattern of inheritance. The gene for WS, wolfram syndrome 1 gene (WFS1), is located on human chromosome 4p16.1 and encodes a transmembrane protein. To date, approximately 230 mutations in WFS1 have been confirmed, in which nonsynonymous single nucleotide polymorphisms (nsSNPs) are the most common forms of genetic variation. Nonetheless, there is poor knowledge on the relationship between SNP genotype and phenotype in other nsSNPs of the WFS1 gene. Here, we analysed 395 nsSNPs associated with the WFS1 gene using different computational methods and identified 20 nsSNPs to be potentially pathogenic. Furthermore, to identify the amino acid distributions and significances of pathogenic nsSNPs in the protein of WFS1, its transmembrane domain was constructed by the TMHMM server, which suggested that mutations outside of the TMhelix could have more effects on protein function. The predicted pathogenic mutations for the nsSNPs of the WFS1 gene provide an excellent guide for screening pathogenic mutations.

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Wfs1‐deficient animals have brain‐region‐specific changes of Na⁺, K⁺‐ATPase activity and mRNA expression of α₁ and β₁ subunits

Cited by 11 publications

References 42 publications

Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease

Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease

Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research

Phenotype Prediction of Pathogenic Nonsynonymous Single Nucleotide Polymorphisms in WFS1

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