Phenotyping Zebrafish Mutant Models to Assess Candidate Genes Associated with Aortic Aneurysm.

ABSTRACT: (1) Background: Whole Exome Sequencing of patients with thoracic aortic aneurysm often identifies "Variants of Uncertain Significance" (VUS), leading to uncertainty in clinical management. We assess a novel mechanism for potential routine assessment of these genes in TAA patients. Zebrafish are increasingly used as experimental models of disease. Advantages include low cost, rapid maturation, and physical transparency, permitting direct microscopic assessment. (2) Methods: Zebrafish loss of function mutations were generated using a CRISPRC/CAS9 approach for EMILIN1 and MIB1 genes similar to VUSs identified in clinical testing. Additionally, "positive control" mutants were constructed for known deleterious variants in FBN1 (Marfan's) and COL1A2, COL5A1, COL5A2 (Ehlers-Danlos). Zebrafish emb

SUBMITTER: Prendergast A 

PROVIDER: S-EPMC8775119 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature