Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotype
<p>Abstract</p> <p>Background</p> <p>Myostatin, a member of the TGFβ superfamily, is well known as a potent and specific negative regulator of muscle growth. Targeting the myostatin signalling pathway may offer promising therapeutic strategies for the treatment of muscl...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-10-01
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| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/13/541 |
| _version_ | 1811248892573908992 |
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| author | Monestier Olivier Brun Caroline Heu Katy Passet Bruno Malhouroux Mélanie Magnol Laetitia Vilotte Jean-Luc Blanquet Véronique |
| author_facet | Monestier Olivier Brun Caroline Heu Katy Passet Bruno Malhouroux Mélanie Magnol Laetitia Vilotte Jean-Luc Blanquet Véronique |
| author_sort | Monestier Olivier |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Myostatin, a member of the TGFβ superfamily, is well known as a potent and specific negative regulator of muscle growth. Targeting the myostatin signalling pathway may offer promising therapeutic strategies for the treatment of muscle-wasting disorders. In the last decade, various myostatin-binding proteins have been identified to be able to inhibit myostatin activity. One of these is GASP1 (Growth and Differentiation Factor-Associated Serum Protein-1), a protein containing a follistatin domain as well as multiple domains associated with protease inhibitors. Despite <it>in vitro</it> data, remarkably little is known about <it>in vivo</it> functions of <it>Gasp1</it>. To further address the role of GASP1 during mouse development and in adulthood, we generated a gain-of-function transgenic mouse model that overexpresses <it>Gasp1</it> under transcriptional control of the human cytomegalovirus immediate-early promoter/enhancer.</p> <p>Results</p> <p>Overexpression of <it>Gasp1</it> led to an increase in muscle mass observed not before day 15 of postnatal life. The surGasp1 transgenic mice did not display any other gross abnormality. Histological and morphometric analysis of surGasp1 <it>rectus femoris</it> muscles revealed an increase in myofiber size without a corresponding increase in myofiber number. Fiber-type distribution was unaltered. Interestingly, we do not detect a change in total fat mass and lean mass. These results differ from those for myostatin knockout mice, transgenic mice overexpressing the myostatin propeptide or follistatin which exhibit both muscle hypertrophy and hyperplasia, and show minimal fat deposition.</p> <p>Conclusions</p> <p>Altogether, our data give new insight into the <it>in vivo</it> functions of <it>Gasp1</it>. As an extracellular regulatory factor in the myostatin signalling pathway, additional studies on GASP1 and its homolog GASP2 are required to elucidate the crosstalk between the different intrinsic inhibitors of the myostatin.</p> |
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| format | Article |
| id | doaj.art-a703e9cfe5fa4e85b51be3d29ac439bd |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-12T15:36:53Z |
| publishDate | 2012-10-01 |
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| series | BMC Genomics |
| spelling | doaj.art-a703e9cfe5fa4e85b51be3d29ac439bd2022-12-22T03:26:56ZengBMCBMC Genomics1471-21642012-10-0113154110.1186/1471-2164-13-541Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotypeMonestier OlivierBrun CarolineHeu KatyPasset BrunoMalhouroux MélanieMagnol LaetitiaVilotte Jean-LucBlanquet Véronique<p>Abstract</p> <p>Background</p> <p>Myostatin, a member of the TGFβ superfamily, is well known as a potent and specific negative regulator of muscle growth. Targeting the myostatin signalling pathway may offer promising therapeutic strategies for the treatment of muscle-wasting disorders. In the last decade, various myostatin-binding proteins have been identified to be able to inhibit myostatin activity. One of these is GASP1 (Growth and Differentiation Factor-Associated Serum Protein-1), a protein containing a follistatin domain as well as multiple domains associated with protease inhibitors. Despite <it>in vitro</it> data, remarkably little is known about <it>in vivo</it> functions of <it>Gasp1</it>. To further address the role of GASP1 during mouse development and in adulthood, we generated a gain-of-function transgenic mouse model that overexpresses <it>Gasp1</it> under transcriptional control of the human cytomegalovirus immediate-early promoter/enhancer.</p> <p>Results</p> <p>Overexpression of <it>Gasp1</it> led to an increase in muscle mass observed not before day 15 of postnatal life. The surGasp1 transgenic mice did not display any other gross abnormality. Histological and morphometric analysis of surGasp1 <it>rectus femoris</it> muscles revealed an increase in myofiber size without a corresponding increase in myofiber number. Fiber-type distribution was unaltered. Interestingly, we do not detect a change in total fat mass and lean mass. These results differ from those for myostatin knockout mice, transgenic mice overexpressing the myostatin propeptide or follistatin which exhibit both muscle hypertrophy and hyperplasia, and show minimal fat deposition.</p> <p>Conclusions</p> <p>Altogether, our data give new insight into the <it>in vivo</it> functions of <it>Gasp1</it>. As an extracellular regulatory factor in the myostatin signalling pathway, additional studies on GASP1 and its homolog GASP2 are required to elucidate the crosstalk between the different intrinsic inhibitors of the myostatin.</p>http://www.biomedcentral.com/1471-2164/13/541 |
| spellingShingle | Monestier Olivier Brun Caroline Heu Katy Passet Bruno Malhouroux Mélanie Magnol Laetitia Vilotte Jean-Luc Blanquet Véronique Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotype BMC Genomics |
| title | Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotype |
| title_full | Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotype |
| title_fullStr | Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotype |
| title_full_unstemmed | Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotype |
| title_short | Ubiquitous <it>Gasp1</it> overexpression in mice leads mainly to a hypermuscular phenotype |
| title_sort | ubiquitous it gasp1 it overexpression in mice leads mainly to a hypermuscular phenotype |
| url | http://www.biomedcentral.com/1471-2164/13/541 |
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