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Using Caenorhabditis elegans as a Model System to Study Protein Homeostasis in a Multicellular Organism
Published on: December 18, 2013
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A human progeria-associated BAF-1 mutation modulates gene expression and accelerates aging in C. elegans
Raquel Romero-Bueno1, Adrián Fragoso-Luna1, Cristina Ayuso1
1Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Pablo de Olavide, Junta de Andalucía, Carretera de Utrera, km 1, 41013, Sevilla, Spain.
The EMBO Journal
|October 4, 2024
Summary
A specific mutation in the Barrier to Autointegration Factor (BAF) protein causes Néstor-Guillermo Progeria Syndrome (NGPS). This study developed a C. elegans model showing altered gene expression and nuclear changes, revealing NGPS mechanisms.
Area of Science:
- Cell Biology
- Genetics
- Aging Research
Background:
- Nuclear envelope alterations are linked to laminopathies, a group of rare diseases.
- Néstor-Guillermo Progeria Syndrome (NGPS) is a premature aging condition caused by a specific mutation in the human nuclear envelope protein BAF (Barrier to Autointegration Factor).
- The underlying mechanisms of NGPS, including growth retardation and skeletal defects, remain largely unknown.
Purpose of the Study:
- To generate a novel in vivo model for NGPS using C. elegans.
- To investigate the molecular mechanisms by which the A12T BAF mutation leads to NGPS phenotypes.
- To explore the role of BAF chromatin association in gene expression and disease pathogenesis.
Main Methods:
- Generated a C. elegans model with a modified baf-1 locus mimicking the human NGPS mutation (baf-1(G12T)).
- Assessed phenotypes including fertility, lifespan, stress resistance, and nuclear morphology during aging.
- Performed tissue-specific chromatin binding and transcriptome analyses.
Main Results:
- The baf-1(G12T) mutant worms exhibited phenotypes related to fertility, lifespan, and stress resistance.
- Nuclear morphology deteriorated more rapidly with age in mutant worms compared to wild-type, mirroring a hallmark of progeria.
- Reduced lamin accumulation at the nuclear envelope was observed in mutant worms.
- Altered BAF-1 chromatin association was linked to deregulation of numerous genes, suggesting a role in NGPS pathogenesis.
Conclusions:
- The C. elegans baf-1(G12T) model effectively recapitulates key aspects of NGPS.
- Altered chromatin association of BAF protein and subsequent changes in gene expression are likely drivers of NGPS phenotypes.
- This study provides insights into the molecular mechanisms underlying NGPS and related laminopathies.
