title: Ubiquitous Gasp1 overexpression in mice leads mainly to a hypermuscular phenotype.
abstract: BACKGROUND
  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 in vitro data, remarkably little is known about in vivo functions of Gasp1. To further address the role of GASP1 during mouse development and in adulthood, we generated a gain-of-function transgenic mouse model that overexpresses Gasp1 under transcriptional control of the human cytomegalovirus immediate-early promoter/enhancer.
  
  
  RESULTS
  Overexpression of Gasp1 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 rectus femoris 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.
  
  
  CONCLUSIONS
  Altogether, our data give new insight into the in vivo functions of Gasp1. 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.
authors.affiliation: INRA, UMR1061 Unité de Génétique Moléculaire Animale, Limoges, 87060, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Monestier
authors.forename: Caroline
authors.initials: C
authors.lastname: Brun
authors.forename: Katy
authors.initials: K
authors.lastname: Heu
authors.forename: Bruno
authors.initials: B
authors.lastname: Passet
authors.forename: Mélanie
authors.initials: M
authors.lastname: Malhouroux
authors.forename: Laetitia
authors.initials: L
authors.lastname: Magnol
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanquet
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D003587:Cytomegalovirus / Q000235:genetics; D038681:Follistatin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009122:Muscle Hypertonia / Q000235:genetics* / Q000378:metabolism; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D052097:Quadriceps Muscle / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
chemical_list: D000956:Antigens, Viral; D002352:Carrier Proteins; D038681:Follistatin; C479636:Gprasp1 protein, mouse; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055435:Myostatin; D012333:RNA, Messenger; C044582:immediate-early proteins, cytomegalovirus