{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:01:01Z","timestamp":1792213261289,"version":"4.4.0"},"reference-count":85,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Wolfram Syndrome (WFS) is a rare, autosomal, recessive neurogenetic disorder that affects many organ systems. It is characterised by diabetes insipidus, diabetes mellites, optic atrophy, and deafness and, therefore, is also known as DIDMOAD. Nearly 15,000\u201330,000 people are affected by WFS worldwide, and, on average, patients suffering from WFS die at 30 years of age, usually from central respiratory failure caused by massive brain atrophy. The more prevalent of the two kinds of WFS is WFS1, which is a monogenic disease and caused by the loss of the WFS1 gene, whereas WFS2, which is more uncommon, is caused by mutations in the CISD2 gene. Currently, there is no treatment for WFS1 to increase the life expectancy of patients, and the treatments available do not significantly improve their quality of life. Understanding the genetics and the molecular mechanisms of WFS1 is essential to finding a cure. The inability of conventional medications to treat WFS1 points to the need for innovative strategies that must address the fundamental cause: the deletion of the WFS1 gene that leads to the profound ER stress and disturbances in proteostasis. An important approach here is to understand the mechanism of the cell degeneration after the deletion of the WFS1 gene and to describe the differences in these mechanisms for the different tissues. The studies so far have indicated that remarkable clinical heterogeneity is caused by the variable vulnerability caused by WFS1 mutations, and these differences cannot be attributed solely to the positions of mutations in the WFS1 gene. The present review gives a broader overview of the results from genomic studies on the WFS1 mouse model.<\/jats:p>","DOI":"10.3390\/biom13091346","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:14:11Z","timestamp":1693822451000},"page":"1346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Genomics of Wolfram Syndrome 1 (WFS1)"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-6643","authenticated-orcid":false,"given":"Sulev","family":"K\u00f5ks","sequence":"first","affiliation":[{"name":"Perron Institute for Neurological and Translational Science, 8 Verdun Street, Nedlands, WA 6009, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(1986). Didmoad (Wolfram) Syndrome. Lancet, 327, 1075\u20131076.","DOI":"10.1016\/S0140-6736(86)91338-3"},{"key":"ref_2","first-page":"715","article-title":"Diabetes Mellitus and Simple Optic Atrophy among Siblings: Report on Four Cases","volume":"13","author":"Wolfram","year":"1938","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1651-2227.1977.tb15069.x","article-title":"Juvenile diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, atonia of the urinary tract and bladder, and other abnormalities (Wolfram syndrome). A review of 88 cases from the literature with personal observations on 3 new patients","volume":"264","author":"Cremers","year":"1977","journal-title":"Acta Paediatr. Scand. Suppl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/2441","article-title":"A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)","volume":"20","author":"Inoue","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_5","first-page":"941","article-title":"Positional cloning of the gene(WFS1) for Wolfram syndrome","volume":"48","author":"Tanizawa","year":"2000","journal-title":"Rinsho Byori"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/00019616-200010010-00008","article-title":"Wolfram syndrome: Clinical and genetic aspects","volume":"10","author":"Fuqua","year":"2000","journal-title":"Endocrinologist"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1086\/302858","article-title":"Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q","volume":"66","author":"Lidral","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1093\/hmg\/10.5.477","article-title":"WFS1 (Wolfram syndrome 1) gene product: Predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain","volume":"10","author":"Takeda","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","first-page":"818","article-title":"Wolfram Syndrome","volume":"132","author":"Karp","year":"1978","journal-title":"Am. J. Dis. Child."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1056\/NEJM197912203012515","article-title":"Wolfram Syndrome Not HLA Linked","volume":"301","author":"Stanley","year":"1979","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2337\/diacare.6.1.67","article-title":"Diabetes mellitus and optic atrophy in two siblings: A report on a new association and a review of the literature","volume":"6","author":"Khardori","year":"1983","journal-title":"Diabetes Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1136\/adc.60.9.823","article-title":"Association of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. The Wolfram or DIDMOAD syndrome","volume":"60","author":"Najjar","year":"1985","journal-title":"Arch. Dis. Child."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/BF00711771","article-title":"DIDMOAD syndrome; further studies and muscle biochemistry","volume":"18","author":"Barrett","year":"1995","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3175313","DOI":"10.1155\/2018\/3175313","article-title":"Increased Mitochondrial Protein Levels and Bioenergetics in the Musculus Rectus Femoris of Wfs1-Deficient Mice","volume":"2018","author":"Eimre","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_15","first-page":"855","article-title":"Linkage of Wolfram syndrome to chromosome 4p16.1 and evidence for heterogeneity","volume":"59","author":"Collier","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/0140-6736(90)92157-D","article-title":"Psychiatric findings in Wolfram syndrome homozygotes","volume":"336","author":"Swift","year":"1990","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/sj.mp.4000344","article-title":"Predisposition of Wolfram syndrome heterozygotes to psychiatric illness","volume":"3","author":"Swift","year":"1998","journal-title":"Mol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0168-0102(01)00221-8","article-title":"Molecular genetics of bipolar disorder","volume":"40","author":"Kato","year":"2001","journal-title":"Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s004310000704","article-title":"Bleeding tendency in Wolfram syndrome: A newly identified feature with phenotype genotype correlation","volume":"160","author":"Jarrah","year":"2001","journal-title":"Eur. J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.2337\/diabetes.51.4.1287","article-title":"Association studies of genetic variation in the WFS1 gene and type 2 diabetes in U.K. populations","volume":"51","author":"Minton","year":"2002","journal-title":"Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/humu.10258","article-title":"Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease","volume":"22","author":"Cryns","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ymgme.2004.04.012","article-title":"Genetic variations in the WFS1 gene in Japanese with type 2 diabetes and bipolar disorder","volume":"82","author":"Kawamoto","year":"2004","journal-title":"Mol. Genet. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/ng2067","article-title":"Common variants in WFS1 confer risk of type 2 diabetes","volume":"39","author":"Sandhu","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1017\/S1461145704004791","article-title":"Polymorphisms in wolframin (WFS1) gene are possibly related to increased risk for mood disorders","volume":"8","author":"Koido","year":"2005","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1017\/S1461145705005468","article-title":"Analysis of SNP profiles in patients with major depressive disorder","volume":"9","author":"Koks","year":"2006","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12017-008-8056-8","article-title":"Common variations in 4p locus are related to male completed suicide","volume":"11","author":"Must","year":"2009","journal-title":"Neuromolecular. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13052-014-0076-4","article-title":"Congenital central diabetes insipidus and optic atrophy in a Wolfram newborn: Is there a role for WFS1 gene in neurodevelopment?","volume":"40","author":"Ghirardello","year":"2014","journal-title":"Ital. J. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1055\/s-0034-1372582","article-title":"Energy metabolism and thyroid function of mice with deleted wolframin (wfs1) gene","volume":"122","author":"Noormets","year":"2014","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_29","unstructured":"K\u00f5ks, S., Luuk, H., Plaas, M., and Vasar, E. (2008). Wfs1 Protein (Wolframin): Emerging Link between the Emotional Brain and Endocrine Pancreas, Research Signpost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1016\/j.amjmed.2008.09.008","article-title":"The comorbidity of diabetes mellitus and depression","volume":"121","author":"Katon","year":"2008","journal-title":"Am. J. Med."},{"key":"ref_31","unstructured":"Koks, S., Luuk, H., Plaas, M., and Vasar, E. (2008). WFS1 Protein (Wolframin): Emerging Link Between the Emotional Brain and Endocrine Pancreas, Research Signpost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1053\/beem.2001.0149","article-title":"Mitochondrial diabetes, DIDMOAD and other inherited diabetes syndromes","volume":"15","author":"Barrett","year":"2001","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1093\/hmg\/7.13.2021","article-title":"Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein","volume":"7","author":"Strom","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1093\/hmg\/ddm296","article-title":"Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress","volume":"17","author":"Zatyka","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1093\/hmg\/ddg214","article-title":"Wolfram syndrome: Structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product","volume":"12","author":"Hofmann","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1086\/302609","article-title":"Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1","volume":"65","author":"Hardy","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1136\/jmg.34.10.838","article-title":"Wolfram (DIDMOAD) syndrome","volume":"34","author":"Barrett","year":"1997","journal-title":"J. Med. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1136\/adc.73.3.251","article-title":"Growth hormone deficiency and empty sella in DIDMOAD syndrome: An endocrine study","volume":"73","author":"Soliman","year":"1995","journal-title":"Arch. Dis. Child."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1152\/physiolgenomics.90407.2008","article-title":"Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway","volume":"37","author":"Koks","year":"2009","journal-title":"Physiol. Genom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/s41419-018-0406-3","article-title":"Wolfram syndrome: MAMs\u2019 connection?","volume":"9","author":"Delprat","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eaaq1380","DOI":"10.1126\/scisignal.aaq1380","article-title":"ER-mitochondria cross-talk is regulated by the Ca(2+) sensor NCS1 and is impaired in Wolfram syndrome","volume":"11","author":"Angebault","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1152\/physiolgenomics.00122.2012","article-title":"Silencing of the WFS1 gene in HEK cells induces pathways related to neurodegeneration and mitochondrial damage","volume":"45","author":"Koks","year":"2013","journal-title":"Physiol. Genom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4000","DOI":"10.1016\/j.febslet.2006.06.036","article-title":"Wolfram syndrome-associated mutations lead to instability and proteasomal degradation of wolframin","volume":"580","author":"Hofmann","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/sj.mp.4001681","article-title":"Wolframin mutations and hospitalization for psychiatric illness","volume":"10","author":"Swift","year":"2005","journal-title":"Mol. Psychiatry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.arr.2005.03.003","article-title":"The stress system in the human brain in depression and neurodegeneration","volume":"4","author":"Swaab","year":"2005","journal-title":"Ageing Res. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"39609","DOI":"10.1074\/jbc.M507426200","article-title":"WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells","volume":"280","author":"Fonseca","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/cne.21777","article-title":"Distribution of Wfs1 protein in the central nervous system of the mouse and its relation to clinical symptoms of the Wolfram syndrome","volume":"509","author":"Luuk","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1477-7827-7-82","article-title":"Male mice with deleted Wolframin (Wfs1) gene have reduced fertility","volume":"7","author":"Noormets","year":"2009","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.bbr.2008.11.007","article-title":"Wfs1-deficient mice display impaired behavioural adaptation in stressful environment","volume":"198","author":"Luuk","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s13105-010-0048-0","article-title":"Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge","volume":"67","author":"Matto","year":"2011","journal-title":"J. Physiol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12750","DOI":"10.14814\/phy2.12750","article-title":"RNA-sequencing of WFS1-deficient pancreatic islets","volume":"4","author":"Ivask","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ajo.2020.04.012","article-title":"Corneal Abnormalities Are Novel Clinical Feature in Wolfram Syndrome","volume":"217","author":"Waszczykowska","year":"2020","journal-title":"Am. J. Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Waszczykowska, A., Zmyslowska, A., Braun, M., Ivask, M., Koks, S., Jurowski, P., and Mlynarski, W. (2020). Multiple Retinal Anomalies in Wfs1-Deficient Mice. Diagnostics, 10.","DOI":"10.3390\/diagnostics10090607"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ajo.2021.09.030","article-title":"Reduced Corneal Sensitivity With Neuronal Degeneration is a Novel Clinical Feature in Wolfram Syndrome","volume":"236","author":"Waszczykowska","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/hmg\/ddh125","article-title":"Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion","volume":"13","author":"Ishihara","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1007\/s00125-005-1947-4","article-title":"Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis","volume":"48","author":"Riggs","year":"2005","journal-title":"Diabetologia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e81779","DOI":"10.7554\/eLife.81779","article-title":"MCT1-dependent energetic failure and neuroinflammation underlie optic nerve degeneration in Wolfram syndrome mice","volume":"12","author":"Rossi","year":"2023","journal-title":"eLife"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eabh3763","DOI":"10.1126\/scitranslmed.abh3763","article-title":"Activation of the sigma-1 receptor chaperone alleviates symptoms of Wolfram syndrome in preclinical models","volume":"14","author":"Crouzier","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1152\/physiolgenomics.00117.2011","article-title":"Hypothalamic gene expression profile indicates a reduction in G protein signaling in the Wfs1 mutant mice","volume":"43","author":"Koks","year":"2011","journal-title":"Physiol. Genom."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e12660","DOI":"10.14814\/phy2.12660","article-title":"Analysis of metabolic effects of menthol on WFS1-deficient mice","volume":"4","author":"Ehrlich","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1601-183X.2007.00304.x","article-title":"Interpretation of knockout experiments: The congenic footprint","volume":"6","author":"Schalkwyk","year":"2007","journal-title":"Genes Brain Behav."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bbr.2007.10.020","article-title":"Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor deficient mice","volume":"188","author":"Koks","year":"2008","journal-title":"Behav. Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00401-022-02417-4","article-title":"Wolframin is a novel regulator of tau pathology and neurodegeneration","volume":"143","author":"Chen","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev.pharmtox.40.1.235","article-title":"The regulator of G protein signaling family","volume":"40","author":"Zheng","year":"2000","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Borges, J.I., Suster, M.S., and Lymperopoulos, A. (2023). Cardiac RGS Proteins in Human Heart Failure and Atrial Fibrillation: Focus on RGS4. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076136"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"pe2","DOI":"10.1126\/stke.3702007pe2","article-title":"RGS proteins: Swiss army knives in seven-transmembrane domain receptor signaling networks","volume":"2007","author":"Heximer","year":"2007","journal-title":"Sci STKE"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.neuroscience.2018.01.039","article-title":"Hippocampus and Hypothalamus RNA-sequencing of WFS1-deficient Mice","volume":"374","author":"Ivask","year":"2018","journal-title":"Neuroscience"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Cho, H.W., Jin, H.S., and Eom, Y.B. (2022). FGFRL1 and FGF genes are associated with height, hypertension, and osteoporosis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0273237"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1242\/jcs.03173","article-title":"GBF1, a cis-Golgi and VTCs-localized ARF-GEF, is implicated in ER-to-Golgi protein traffic","volume":"119","author":"Zhao","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1600-0854.2005.00282.x","article-title":"Dissection of membrane dynamics of the ARF-guanine nucleotide exchange factor GBF1","volume":"6","author":"Szul","year":"2005","journal-title":"Traffic"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1073\/pnas.0712224105","article-title":"Unfolded protein response and cell death after depletion of brefeldin A-inhibited guanine nucleotide-exchange protein GBF1","volume":"105","author":"Citterio","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00424-010-0835-z","article-title":"TRPM5 regulates glucose-stimulated insulin secretion","volume":"460","author":"Brixel","year":"2010","journal-title":"Pflugers. Arch."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fnmol.2015.00045","article-title":"Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice","volume":"8","author":"Tein","year":"2015","journal-title":"Front. Mol. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.dib.2018.10.015","article-title":"Proteomic dataset of wolframin-deficient mouse heart and skeletal muscles","volume":"21","author":"Eimre","year":"2018","journal-title":"Data Brief."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s11892-022-01483-y","article-title":"Diabetes Out-of-the-Box: Diabetes Mellitus and Impairment in Hearing and Vision","volume":"22","author":"Gruber","year":"2022","journal-title":"Curr. Diab. Rep"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1210\/er.2015-1116","article-title":"Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes","volume":"37","author":"Yang","year":"2016","journal-title":"Endocr. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/1753-0407.12289","article-title":"Differential promoter activity by nucleotide substitution at a type 2 diabetes genome-wide association study signal upstream of the wolframin gene","volume":"8","author":"Ryu","year":"2016","journal-title":"J. Diabetes"},{"key":"ref_78","first-page":"712","article-title":"Diabetes mellitus, optic nerve atrophy and deafness (Wolfram\u2019s syndrome) in a 29-year-old patient","volume":"31","author":"Hoster","year":"1990","journal-title":"Internist"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3109\/13816819409098867","article-title":"Wolfram syndrome: A report of four cases and review of the literature","volume":"15","author":"Bitoun","year":"1994","journal-title":"Ophthalmic Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/ana.410390312","article-title":"Wolfram syndrome: Hereditary diabetes mellitus with brainstem and optic atrophy","volume":"39","author":"Scolding","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"eaax9106","DOI":"10.1126\/scitranslmed.aax9106","article-title":"Gene-edited human stem cell-derived \u03b2 cells from a patient with monogenic diabetes reverse preexisting diabetes in mice","volume":"12","author":"Maxwell","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"17389","DOI":"10.1073\/pnas.2007136117","article-title":"Calpain inhibitor and ibudilast rescue beta cell functions in a cellular model of Wolfram syndrome","volume":"117","author":"Nguyen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"26330040211039518","DOI":"10.1177\/26330040211039518","article-title":"Wolfram syndrome: New pathophysiological insights and therapeutic strategies","volume":"2","author":"Mishra","year":"2021","journal-title":"Ther. Adv. Rare Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/s41374-020-0436-1","article-title":"A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome","volume":"100","author":"Mahadevan","year":"2020","journal-title":"Lab. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/BF02435965","article-title":"Mitochondrial abnormalities in the DIDMOAD syndrome","volume":"15","author":"Bundey","year":"1992","journal-title":"J. Inherit. Metab. 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