The spatial and developmental expression of mouse Vwa8 (von Willebrand domain-containing protein 8)

Grewe, Brian S.; Richmond, Janet E.; Featherstone, David E.

doi:10.1016/j.gep.2018.04.004

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…However, recently, immunotherapy blocking the effects of negative checkpoint regulators have been shown to affect the central nervous system [ 129 ]. VSIR, in particular, is known to be expressed in microglia and endothelial cells of the central nervous system, with its expression being differentially regulated in ageing, neuroinflammation, and diseases of the central nervous system such as neurodegeneration [ 130 ]. GWAS have linked the human VWA8 to neurological pathologies such as autism, bipolar disorder, and comorbid migraine [ 130 ].…”

Section: Discussionmentioning

confidence: 99%

“…VSIR, in particular, is known to be expressed in microglia and endothelial cells of the central nervous system, with its expression being differentially regulated in ageing, neuroinflammation, and diseases of the central nervous system such as neurodegeneration [ 130 ]. GWAS have linked the human VWA8 to neurological pathologies such as autism, bipolar disorder, and comorbid migraine [ 130 ]. The only top-DMR present in a promoter region was associated with the RCC1 gene .…”

Section: Discussionmentioning

confidence: 99%

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An enriched maternal environment and stereotypies of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets

et al. 2023

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Epigenetic mechanisms are important modulators of neurodevelopmental outcomes in the offspring of animals challenged during pregnancy. Pregnant sows living in a confined environment are challenged with stress and lack of stimulation which may result in the expression of stereotypies (repetitive behaviours without an apparent function). Little attention has been devoted to the postnatal effects of maternal stereotypies in the offspring. We investigated how the environment and stereotypies of pregnant sows affected the neuro-epigenome of their piglets. We focused on the amygdala, frontal cortex, and hippocampus, brain regions related to emotionality, learning, memory, and stress response. Differentially methylated regions (DMRs) were investigated in these brain regions of male piglets born from sows kept in an enriched vs a barren environment. Within the latter group of piglets, we compared the brain methylomes of piglets born from sows expressing stereotypies vs sows not expressing stereotypies. DMRs emerged in each comparison. While the epigenome of the hippocampus and frontal cortex of piglets is mainly affected by the maternal environment, the epigenome of the amygdala is mainly affected by maternal stereotypies. The molecular pathways and mechanisms triggered in the brains of piglets by maternal environment or stereotypies are different, which is reflected on the differential gene function associated to the DMRs found in each piglets’ brain region . The present study is the first to investigate the neuro-epigenomic effects of maternal enrichment in pigs’ offspring and the first to investigate the neuro-epigenomic effects of maternal stereotypies in the offspring of a mammal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An enriched maternal environment and stereotypies of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets

et al. 2023

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“…VWA8 is a mitochondrial and peroxisomal protein reported to play a key role in regulating ATPase activity inside the cell. Using P7 and P56, mouse tissues VWA8a and VWA8b were expressed in the cerebellum, left and right hemisphere, heart, lungs, spleen, and upper and lower limbs (Grewe et al, 2018). It has been observed that VWA8 possesses ATPase activity, suggesting its involvement in the energy-consuming biological processes in the body (Luo et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Mutated VWA8 Is Associated With Developmental Delay, Microcephaly, and Scoliosis and Plays a Novel Role in Early Development and Skeletal Morphogenesis in Zebrafish

Umair

Khan

Aldrees

et al. 2021

Front. Cell Dev. Biol.

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Von Willebrand A domain-containing protein 8 (VWA8), also named KIAA0564, is a poorly characterized, mitochondrial matrix-targeted protein having a putative ATPase activity. VWA8 is comprising of ATPase-associated domains and a VWFA domain associated with ATPase activity inside the cell. In the present study, we describe a large consanguineous family of Saudi origin segregating a complex developmental syndrome in an autosomal recessive fashion. All the affected individuals exhibited severe developmental disorders. DNA from three patients was subjected to whole-exome sequencing followed by Sanger sequencing. VWA8 knock-down zebrafish morpholinos were used to study the phenotypic effect of this gene on zebrafish development. A homozygous missense variant [c.947A > G; p.(Asp316Gly)] was identified in exon 8 of the VWA8 gene, which perfectly segregated with the disease phenotype. Using zebrafish morpholino, we observed delayed development at an early stage, lack of movement, light sensitivity, severe skeletal deformity such as scoliosis, and facial dysmorphism. This is the first homozygous variant identified in the VWA8 gene underlying global developmental delay, microcephaly, scoliosis, limbs, and cardiovascular malformations in humans. We provide genetic and molecular evidence using zebrafish morpholino for a homozygous variant in the VWA8 gene, associated with such a complex developmental syndrome in humans.

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“…Although the precise function of VWA8 is not known, genome-wide association studies have shown that variation in the VWA8 gene is associated with serum calcium concentrations [1,2], autism [3], and bipolar disorder with comorbid migraine [4], as well as acute myeloid leukemia [5]. A study in mice showed the full-length VWA8a is highly expressed relative to the truncated VWA8b transcript across all developmental time points and tissues analyzed [6]. VWA8 protein is significantly downregulated in breast cancer brain metastases and the expression of VWA8 in brain metastases is significantly decreased [7].…”

Section: Introductionmentioning

confidence: 99%

Von Willebrand factor A domain-containing protein 8 (VWA8) localizes to the matrix side of the inner mitochondrial membrane

Luo

Sand

et al. 2020

Biochemical and Biophysical Research Communications

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VWA8 is a poorly characterized mitochondrial AAA+ ATPase protein. However, the specific submitochondrial localization of VWA8 remains unclear. The purpose of this study was to determine the specific submitochondrial compartment within which VWA8 resides in order to provide more insight into the function of this protein. Bioinformatics analysis showed that VWA8 has a 34 amino acid N-terminal Matrix-Targeting Signal (MTS) that is similar to those in proteins known to localize to the mitochondrial matrix. Experiments in C2C12 mouse myoblasts using confocal microscopy showed that deletion of the VWA8 MTS (vMTS) resulted in cytosolic, rather than mitochondrial, localization of VWA8. Biochemical analysis using differential subfractionation of mitochondria isolated from rat liver showed that VWA8 localizes to the matrix side of inner mitochondrial membrane, similar to the inner mitochondrial membrane protein Electron Transfer Flavoprotein-ubiquinone Oxidoreductase (ETFDH). The results of these experiments show that the vMTS is essential for localization to the mitochondrial matrix and that once there, VWA8 localizes to the matrix side of inner mitochondrial membrane.

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The spatial and developmental expression of mouse Vwa8 (von Willebrand domain-containing protein 8)

Cited by 6 publications

References 32 publications

An enriched maternal environment and stereotypies of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets

An enriched maternal environment and stereotypies of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets

Mutated VWA8 Is Associated With Developmental Delay, Microcephaly, and Scoliosis and Plays a Novel Role in Early Development and Skeletal Morphogenesis in Zebrafish

Von Willebrand factor A domain-containing protein 8 (VWA8) localizes to the matrix side of the inner mitochondrial membrane

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