GEO series
The p.Ser143Pro lamin A/C mutation leads to dilated cardiomyopathy and activates the unfolded protein response pathway in a knock-in mouse model
GSE330200
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
19 samples
Submitted 2026/06/18
Platform GPL24676Platform GPL24247
Summary
Dilated cardiomyopathy (DCM) is characterized by progressive ventricular dilation, systolic dysfunction, and an increased risk of arrythmias and sudden cardiac arrest. Variants in the LMNA gene, which encodesing for the nuclear lamins A and C, have been linked to familial form of the disease and the founder variant p.Ser143Pro is particularly common among Finnish DCM patients. To clarify elucidate the complex and poorly understood pathogenic mechanisms behind LMNA-related DCM, we generated a mouse model carrying the p.Ser143Pro mutation in the Lmna gene. All genetically modified mice appeared normal at birth. However, based on echocardiographyic, necropsy, B-type natriuretic peptide (Nppb) expression levels, and histopathological data, homozygous males developed progressive left ventricular dilatation, myocardial fibrosis, and cardiac failure after six months of age, with all succumbing before ten months. A reduced disease penetrance was observed in heterozygous male and homozygous female mice, with one-year survival rates of 40% and 60%, respectively. No signs of skeletal myopathy were observed in mice carrying the mutation. Whole-transcriptome RNA sequencing analysis of left ventricular cardiac tissue from asymptomatic two-month-old homozygous male mice revealed an upregulation of classical heart failure markers, such as atrial natriuretic peptide (Nppa ) and myosin heavy chain β (Myh7), and an elevated unfolded protein response signaling, as shown by elevated DNA damage-inducible transcript 3 (Ddit), Bcl-2-associated athanogene 3 (Bag3) and CCAAT/enhancer-binding protein beta (Cebpb) levels especially in the homozygous males compared to wild-type mice. In conclusion, p.Ser143Pro-Lmna mice closely mimic the clinical phenotype observed in patients with the p.Ser143Pro LMNA variant and offerserve as a valuablepotential in vivo model for investigatingstudying the underlying pathogenic mechanisms of LMNA-related DCM in greater detail.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE330200_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 19 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1463114 and SRA study SRP698257. Searching any of these in the dataset finder brings you back here.
Study design
6 × mice, heart, male, wt, vs 6 × mice, heart, male, hez, vs 6 × mice, heart, male, hom,
Supports a between-group comparison across 18 samples.
3 replicated groups read from 19 sample titles; they account for 18 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9721150 mice, heart, male, wt, rep1
- GSM9721151 mice, heart, male, wt, rep2
- GSM9721152 mice, heart, male, wt, rep3
- GSM9721153 mice, heart, male, wt, rep4
- GSM9721154 mice, heart, male, wt, rep5
- GSM9721155 mice, heart, male, wt, rep6
- GSM9721156 mice, heart, male, hez, rep1
- GSM9721157 mice, heart, male, hez, rep2
- GSM9721158 mice, heart, male, hez, rep3
- GSM9721159 mice, heart, male, hez, rep4
- GSM9721160 mice, heart, male, hez, rep5
- GSM9721161 mice, heart, male, hez, rep6
- GSM9721162 mice, heart, male, hom, rep1
- GSM9721163 mice, heart, male, hom, rep2
- GSM9721164 mice, heart, male, hom, rep3
- GSM9721165 mice, heart, male, hom, rep4
- GSM9721166 mice, heart, male, hom, rep5
- GSM9721167 mice, heart, male, hom, rep6
- GSM9721168 ctrl human brain
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