Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac Phenotype
The <i>Cdkn2a</i> locus is one of the most studied tumor suppressor loci in the context of several cancer types. However, in the last years, its expression has also been linked to terminal differentiation and the activation of the senescence program in different cellular subtypes. Knock-...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/4/538 |
| _version_ | 1797538602431807488 |
|---|---|
| author | Gloria Pegoli Marika Milan Pierluigi Giuseppe Manti Andrea Bianchi Federica Lucini Philina Santarelli Claudia Bearzi Roberto Rizzi Chiara Lanzuolo |
| author_facet | Gloria Pegoli Marika Milan Pierluigi Giuseppe Manti Andrea Bianchi Federica Lucini Philina Santarelli Claudia Bearzi Roberto Rizzi Chiara Lanzuolo |
| author_sort | Gloria Pegoli |
| collection | DOAJ |
| description | The <i>Cdkn2a</i> locus is one of the most studied tumor suppressor loci in the context of several cancer types. However, in the last years, its expression has also been linked to terminal differentiation and the activation of the senescence program in different cellular subtypes. Knock-out (KO) of the entire locus enhances the capability of stem cells to proliferate in some tissues and respond to severe physiological and non-physiological damages in different organs, including the heart. Emery–Dreifuss muscular dystrophy (EDMD) is characterized by severe contractures and muscle loss at the level of skeletal muscles of the elbows, ankles and neck, and by dilated cardiomyopathy. We have recently demonstrated, using the <i>LMNA</i> Δ<i>8–11</i> murine model of Emery–Dreifuss muscular dystrophy (EDMD), that dystrophic muscle stem cells prematurely express non-lineage-specific genes early on during postnatal growth, leading to rapid exhaustion of the muscle stem cell pool. Knock-out of the <i>Cdkn2a</i> locus in EDMD dystrophic mice partially restores muscle stem cell properties. In the present study, we describe the cardiac phenotype of the <i>LMNA</i> Δ<i>8–11</i> mouse model and functionally characterize the effects of KO of the <i>Cdkn2a</i> locus on heart functions and life expectancy. |
| first_indexed | 2024-03-10T12:33:45Z |
| format | Article |
| id | doaj.art-4fa67a5f517d49748c35a7e8b58b8510 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T12:33:45Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-4fa67a5f517d49748c35a7e8b58b85102023-11-21T14:26:23ZengMDPI AGBiomolecules2218-273X2021-04-0111453810.3390/biom11040538Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac PhenotypeGloria Pegoli0Marika Milan1Pierluigi Giuseppe Manti2Andrea Bianchi3Federica Lucini4Philina Santarelli5Claudia Bearzi6Roberto Rizzi7Chiara Lanzuolo8Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyIstituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyIstituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyIstituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyIstituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyIstituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyIstituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyIstituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, ItalyThe <i>Cdkn2a</i> locus is one of the most studied tumor suppressor loci in the context of several cancer types. However, in the last years, its expression has also been linked to terminal differentiation and the activation of the senescence program in different cellular subtypes. Knock-out (KO) of the entire locus enhances the capability of stem cells to proliferate in some tissues and respond to severe physiological and non-physiological damages in different organs, including the heart. Emery–Dreifuss muscular dystrophy (EDMD) is characterized by severe contractures and muscle loss at the level of skeletal muscles of the elbows, ankles and neck, and by dilated cardiomyopathy. We have recently demonstrated, using the <i>LMNA</i> Δ<i>8–11</i> murine model of Emery–Dreifuss muscular dystrophy (EDMD), that dystrophic muscle stem cells prematurely express non-lineage-specific genes early on during postnatal growth, leading to rapid exhaustion of the muscle stem cell pool. Knock-out of the <i>Cdkn2a</i> locus in EDMD dystrophic mice partially restores muscle stem cell properties. In the present study, we describe the cardiac phenotype of the <i>LMNA</i> Δ<i>8–11</i> mouse model and functionally characterize the effects of KO of the <i>Cdkn2a</i> locus on heart functions and life expectancy.https://www.mdpi.com/2218-273X/11/4/538Emery–Dreifuss muscular dystrophy<i>Cdkn2a</i> locusLamin A/Cp16<sup>INK4a</sup>heartdilated cardiomyopathy |
| spellingShingle | Gloria Pegoli Marika Milan Pierluigi Giuseppe Manti Andrea Bianchi Federica Lucini Philina Santarelli Claudia Bearzi Roberto Rizzi Chiara Lanzuolo Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac Phenotype Biomolecules Emery–Dreifuss muscular dystrophy <i>Cdkn2a</i> locus Lamin A/C p16<sup>INK4a</sup> heart dilated cardiomyopathy |
| title | Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac Phenotype |
| title_full | Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac Phenotype |
| title_fullStr | Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac Phenotype |
| title_full_unstemmed | Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac Phenotype |
| title_short | Role of <i>Cdkn2a</i> in the Emery–Dreifuss Muscular Dystrophy Cardiac Phenotype |
| title_sort | role of i cdkn2a i in the emery dreifuss muscular dystrophy cardiac phenotype |
| topic | Emery–Dreifuss muscular dystrophy <i>Cdkn2a</i> locus Lamin A/C p16<sup>INK4a</sup> heart dilated cardiomyopathy |
| url | https://www.mdpi.com/2218-273X/11/4/538 |
| work_keys_str_mv | AT gloriapegoli roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT marikamilan roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT pierluigigiuseppemanti roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT andreabianchi roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT federicalucini roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT philinasantarelli roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT claudiabearzi roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT robertorizzi roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype AT chiaralanzuolo roleoficdkn2aiintheemerydreifussmusculardystrophycardiacphenotype |