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Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins.
Nucleus. 2011 May-Jun; 2(3):195-207.N

Abstract

A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNA(GT-/-)) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies.

Authors+Show Affiliations

Heart Failure Research Center and Department of Cardiology, Maastricht University Medical Centre, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21818413

Citation

Kubben, Nard, et al. "Post-natal Myogenic and Adipogenic Developmental: Defects and Metabolic Impairment Upon Loss of A-type Lamins." Nucleus (Austin, Tex.), vol. 2, no. 3, 2011, pp. 195-207.
Kubben N, Voncken JW, Konings G, et al. Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins. Nucleus. 2011;2(3):195-207.
Kubben, N., Voncken, J. W., Konings, G., van Weeghel, M., van den Hoogenhof, M. M., Gijbels, M., van Erk, A., Schoonderwoerd, K., van den Bosch, B., Dahlmans, V., Calis, C., Houten, S. M., Misteli, T., & Pinto, Y. M. (2011). Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins. Nucleus (Austin, Tex.), 2(3), 195-207. https://doi.org/10.4161/nucl.2.3.15731
Kubben N, et al. Post-natal Myogenic and Adipogenic Developmental: Defects and Metabolic Impairment Upon Loss of A-type Lamins. Nucleus. 2011 May-Jun;2(3):195-207. PubMed PMID: 21818413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins. AU - Kubben,Nard, AU - Voncken,Jan Willem, AU - Konings,Gonda, AU - van Weeghel,Michel, AU - van den Hoogenhof,Maarten Mg, AU - Gijbels,Marion, AU - van Erk,Arie, AU - Schoonderwoerd,Kees, AU - van den Bosch,Bianca, AU - Dahlmans,Vivian, AU - Calis,Chantal, AU - Houten,Sander M, AU - Misteli,Tom, AU - Pinto,Yigal M, PY - 2011/01/14/received PY - 2011/04/01/revised PY - 2011/04/05/accepted PY - 2011/8/6/entrez PY - 2011/8/6/pubmed PY - 2012/4/10/medline KW - LMNA KW - cardiac hypertrophy KW - differentiation KW - knock-out mouse KW - lamin A KW - laminopathies KW - muscular dystrophy SP - 195 EP - 207 JF - Nucleus (Austin, Tex.) JO - Nucleus VL - 2 IS - 3 N2 - A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNA(GT-/-)) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. SN - 1949-1042 UR - https://www.unboundmedicine.com/medline/citation/21818413/Post_natal_myogenic_and_adipogenic_developmental:_defects_and_metabolic_impairment_upon_loss_of_A_type_lamins_ L2 - http://www.tandfonline.com/doi/full/10.4161/nucl.2.3.15731 DB - PRIME DP - Unbound Medicine ER -