Journal article
Drosophila Models Reveal Properties of Mutant Lamins That Give Rise to Distinct Diseases
Cells (Basel, Switzerland), Vol.12(8), 1142
04/12/2023
DOI: 10.3390/cells12081142
PMCID: PMC10136830
PMID: 37190051
Abstract
Mutations in the
LMNA
gene cause a collection of diseases known as laminopathies, including muscular dystrophies, lipodystrophies, and early-onset aging syndromes. The
LMNA
gene encodes A-type lamins, lamins A/C, intermediate filaments that form a meshwork underlying the inner nuclear membrane. Lamins have a conserved domain structure consisting of a head, coiled-coil rod, and C-terminal tail domain possessing an Ig-like fold. This study identified differences between two mutant lamins that cause distinct clinical diseases. One of the
LMNA
mutations encodes lamin A/C p.R527P and the other codes lamin A/C p.R482W, which are typically associated with muscular dystrophy and lipodystrophy, respectively. To determine how these mutations differentially affect muscle, we generated the equivalent mutations in the
Drosophila Lamin C (LamC)
gene, an orthologue of human
LMNA
. The muscle-specific expression of the R527P equivalent showed cytoplasmic aggregation of LamC, a reduced larval muscle size, decreased larval motility, and cardiac defects resulting in a reduced adult lifespan. By contrast, the muscle-specific expression of the R482W equivalent caused an abnormal nuclear shape without a change in larval muscle size, larval motility, and adult lifespan compared to controls. Collectively, these studies identified fundamental differences in the properties of mutant lamins that cause clinically distinct phenotypes, providing insights into disease mechanisms.
Details
- Title: Subtitle
- Drosophila Models Reveal Properties of Mutant Lamins That Give Rise to Distinct Diseases
- Creators
- Sydney G. Walker - University of IowaChristopher J. Langland - University of IowaJill Viles - Independent Researcher, Gowrie, IA 50543, USALaura A. Hecker - Clarke UniversityLori L. Wallrath - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cells (Basel, Switzerland), Vol.12(8), 1142
- DOI
- 10.3390/cells12081142
- PMID
- 37190051
- PMCID
- PMC10136830
- NLM abbreviation
- Cells
- eISSN
- 2073-4409
- Publisher
- MDPI
- Grant note
- R21 AR075193 / NIH NIAMS
- Language
- English
- Date published
- 04/12/2023
- Academic Unit
- Biochemistry and Molecular Biology; University College Courses
- Record Identifier
- 9984399640802771
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