Diverse species-specific phenotypic consequences of loss of function sorting nexin 14 mutations
| العنوان: | Diverse species-specific phenotypic consequences of loss of function sorting nexin 14 mutations |
|---|---|
| المؤلفون: | Miho Ishida, Philip Stanier, Daniyal J. Jafree, Emma Peskett, Claire Walsh, Jason Rihel, Cristina Alemán-Charlet, Kaitlyn M. Eckert, Sanchari Datta, Rimante Seselgyte, Thomas A. Hawkins, Marian Seda, Jeffrey G. McDonald, Hanaa Hariri, Lydia Teboul, Charalambos Demetriou, Gideon Pomeranz, Gudrun E. Moore, Letizia Vestito, Dale Bryant, W. Mike Henne, Maria Bitner-Glindzicz, Myriam Hemberger, Dagan Jenkins, Constance Maurer, Marcus Ghosh, James Cleak |
| المصدر: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Molecular biology, Placenta, lcsh:Medicine, Diseases, Pathogenesis, medicine.disease_cause, Animals, Genetically Modified, Mice, 0302 clinical medicine, Pregnancy, lcsh:Science, Zebrafish, Sorting Nexins, Phospholipids, 0303 health sciences, Mutation, Multidisciplinary, Molecular medicine, Biological techniques, Cell Differentiation, Phenotype, Cell biology, Trophoblasts, Neurology, Models, Animal, Spinocerebellar ataxia, Female, Embryonic Development, Biology, Article, 03 medical and health sciences, Developmental biology, medicine, Genetics, Animals, Humans, Spinocerebellar Ataxias, Fetal Viability, Gene, Loss function, 030304 developmental biology, lcsh:R, Lipid metabolism, biology.organism_classification, medicine.disease, Lipid Metabolism, Mice, Inbred C57BL, Sorting nexin, 030104 developmental biology, lcsh:Q, 030217 neurology & neurosurgery, Neuroscience |
| الوصف: | Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) in both humans and dogs. SCAR20 is understood to involve subcellular disruption to autophagy and lipid metabolism. Previously reported studies on the phenotypic consequences of SNX14 mutations have been limited to in vitro investigation of patient-derived dermal fibroblasts, laboratory engineered cell lines and developmental analysis of zebrafish morphants. In addition, studies have investigated the biochemical roles of SNX14 homologues Snz (Drosophila) and Mdm1 (yeast) which have demonstrated an important role during lipid biogenesis. This study investigates the impact of constitutive Snx14 mutations in laboratory species: mice and zebrafish. Loss of SNX14 in mice was found to be embryonic lethal around mid-gestation. This is due to placental pathology that involves severe disruption to syncytiotrophoblast cell differentiation. Zebrafish carrying a homozygous, maternal zygotic snx14 genetic loss-of-function mutation contrasts with other vertebrates, being both viable and anatomically normal. Whilst no obvious behavioural effects were observed, elevated levels of neutral lipids and phospholipids resemble previously reported effects on lipid homeostasis in other species. The biochemical role of SNX14 therefore appears largely conserved through evolution while the overall consequences of loss of function varies considerably between species. New mouse and zebrafish models therefore provide valuable insights into the functional importance of SNX14 with distinct opportunities for investigating its cellular and metabolic function in vivo. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c5088837813b63ac8b07f9923f25c772Test http://hdl.handle.net/10044/1/90147Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c5088837813b63ac8b07f9923f25c772 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |