Caenorhabditis elegans models for striated muscle disorders caused by missense variants of human LMNA

• DOI: 10.1371/journal.pgen.1010895
• Publication Date: 2023-08-25T17:37:07Z
• Authors: Ellen F. Gregory; Shilpi Kalra; Trisha Brock; Gisèle Bonne; G. W. Gant Luxton; Christopher Hopkins; Daniel A. Starr
• Keywords: LMNA

Striated muscle laminopathies caused by missense mutations in the nuclear lamin gene LMNA are characterized cardiac dysfunction and often skeletal defects. Attempts to predict which variants pathogenic understand their physiological effects lag behind variant discovery. We created Caenorhabditis elegans models for striated introducing human of unknown significance at conserved residues within lmn-1 gene. Severe reduced fertility and/or motility C. elegans. Nuclear morphology defects were evident hypodermal nuclei many strains, indicating a loss envelope integrity. Phenotypic severity varied two classes involved disease, but overall, associated with both humans lead more severe phenotypes our model than predicted disrupt function alone. also identified separation allele, lmn-1(R204W), that exhibited normal viability swimming behavior had migration defect. Thus, we established avatars offer insight into mechanisms during development.