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Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle
Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. To investigate the functional role of nebulin in vivo, we generated nebulin-deficient mice by using a Cre knock-in strategy. Lin...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063916/ https://www.ncbi.nlm.nih.gov/pubmed/16769824 http://dx.doi.org/10.1083/jcb.200603119 |
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author | Bang, Marie-Louise Li, Xiaodong Littlefield, Ryan Bremner, Shannon Thor, Andrea Knowlton, Kirk U. Lieber, Richard L. Chen, Ju |
author_facet | Bang, Marie-Louise Li, Xiaodong Littlefield, Ryan Bremner, Shannon Thor, Andrea Knowlton, Kirk U. Lieber, Richard L. Chen, Ju |
author_sort | Bang, Marie-Louise |
collection | PubMed |
description | Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. To investigate the functional role of nebulin in vivo, we generated nebulin-deficient mice by using a Cre knock-in strategy. Lineage studies utilizing this mouse model demonstrated that nebulin is expressed uniformly in all skeletal muscles. Nebulin-deficient mice die within 8–11 d after birth, with symptoms including decreased milk intake and muscle weakness. Although myofibrillogenesis had occurred, skeletal muscle thin filament lengths were up to 25% shorter compared with wild type, and thin filaments were uniform in length both within and between muscle types. Ultrastructural studies also demonstrated a critical role for nebulin in the maintenance of sarcomeric structure in skeletal muscle. The functional importance of nebulin in skeletal muscle function was revealed by isometric contractility assays, which demonstrated a dramatic reduction in force production in nebulin-deficient skeletal muscle. |
format | Text |
id | pubmed-2063916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20639162007-11-29 Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle Bang, Marie-Louise Li, Xiaodong Littlefield, Ryan Bremner, Shannon Thor, Andrea Knowlton, Kirk U. Lieber, Richard L. Chen, Ju J Cell Biol Research Articles Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. To investigate the functional role of nebulin in vivo, we generated nebulin-deficient mice by using a Cre knock-in strategy. Lineage studies utilizing this mouse model demonstrated that nebulin is expressed uniformly in all skeletal muscles. Nebulin-deficient mice die within 8–11 d after birth, with symptoms including decreased milk intake and muscle weakness. Although myofibrillogenesis had occurred, skeletal muscle thin filament lengths were up to 25% shorter compared with wild type, and thin filaments were uniform in length both within and between muscle types. Ultrastructural studies also demonstrated a critical role for nebulin in the maintenance of sarcomeric structure in skeletal muscle. The functional importance of nebulin in skeletal muscle function was revealed by isometric contractility assays, which demonstrated a dramatic reduction in force production in nebulin-deficient skeletal muscle. The Rockefeller University Press 2006-06-19 /pmc/articles/PMC2063916/ /pubmed/16769824 http://dx.doi.org/10.1083/jcb.200603119 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Bang, Marie-Louise Li, Xiaodong Littlefield, Ryan Bremner, Shannon Thor, Andrea Knowlton, Kirk U. Lieber, Richard L. Chen, Ju Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle |
title | Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle |
title_full | Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle |
title_fullStr | Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle |
title_full_unstemmed | Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle |
title_short | Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle |
title_sort | nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063916/ https://www.ncbi.nlm.nih.gov/pubmed/16769824 http://dx.doi.org/10.1083/jcb.200603119 |
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