ArticleHuman molecular genetics2019
Genomic knockout of alms1 in zebrafish recapitulates Alström syndrome and provides insight into metabolic phenotypes.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Consensus clinical management guidelines for Alström syndrome.Orphanet journal of rare diseases · 2020Pooled it
- Characterization of the zebrafish as a model of ATP-sensitive potassium channel hyperinsulinism.BMJ open diabetes research & care · 2024Article
- Role of EP4 factor in paediatric type 1 diabetes mellitus: a comprehensive review focusing on the honeymoon period.Pediatric endocrinology, diabetes, and metabolism · 2024Review
- Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.Cellular and molecular neurobiology · 2023Review
- Ancestry-driven metabolite variation provides insights into disease states in admixed populations.Genome medicine · 2023Article
- Primary Cilia in Pancreatic β- and α-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme.Frontiers in endocrinology · 2022Review
- Novel Mutations of the ALMS1 Gene in Patients with Alström Syndrome.Internal medicine (Tokyo, Japan) · 2021Article
- Recessive ciliopathy mutations in primary endocardial fibroelastosis: a rare neonatal cardiomyopathy in a case of Alstrom syndrome.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Discovery of ciliary G protein-coupled receptors regulating pancreatic islet insulin and glucagon secretion.Genes & development · 2021Article
- Exocrine pancreas proteases regulate β-cell proliferation in zebrafish ciliopathy models and in murine systems.Biology open · 2021Article
- Alström syndrome: an ultra-rare monogenic disorder as a model for insulin resistance, type 2 diabetes mellitus and obesity.Endocrine · 2021Review
- Article
- A very early diagnosis of Alstrӧm syndrome by next generation sequencing.BMC medical genetics · 2020Article
- Primary Cilium, An Unsung Hero in Maintaining Functional β-cell Population.The Yale journal of biology and medicine · 2019Review
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Authors and funding
11 authors at 3 institutions in 1 country.
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Abstract
Alström syndrome (OMIM #203800) is an autosomal recessive obesity ciliopathy caused by loss-of-function mutations in the ALMS1 gene. In addition to multi-organ dysfunction, such as cardiomyopathy, retinal degeneration and renal dysfunction, the disorder is characterized by high rates of obesity, insulin resistance and early-onset type 2 diabetes mellitus (T2DM). To investigate the underlying mechanisms of T2DM phenotypes, we generated a loss-of-function deletion of alms1 in the zebrafish. We demonstrate conservation of hallmark clinical characteristics alongside metabolic syndrome phenotypes, including a propensity for obesity and fatty livers, hyperinsulinemia and glucose response defects. Gene expression changes in β-cells isolated from alms1-/- mutants revealed changes consistent with insulin hypersecretion and glucose sensing failure, which were corroborated in cultured murine β-cells lacking Alms1. We also found evidence of defects in peripheral glucose uptake and concomitant hyperinsulinemia in the alms1-/- animals. We propose a model in which hyperinsulinemia is the primary and causative defect underlying generation of T2DM associated with alms1 deficiency. These observations support the alms1 loss-of-function zebrafish mutant as a monogenic model for mechanistic interrogation of T2DM phenotypes.
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