GASP-2 overexpressing mice exhibit a hypermuscular phenotype with contrasting molecular effects compared to GASP-1 transgenics.

Muscle atrophy is associated with many diseases including genetic disorders, sarcopenia, or cachexia syndromes. Myostatin (Mstn), a transforming growth factor-beta (TGF-ß) member, plays a key role in skeletal muscle homeostasis as a powerful negative regulator. Over the last decade, about 15 clinical trials aimed at inhibiting the Mstn pathway, failed to produce conclusive results. In this context, we investigated whether growth and differentiation factor-associated serum protein-1 (GASP-1) or GASP-2, two natural inhibitors of Mstn, might represent a potential therapeutic. As we previously reported, mice overexpressing Gasp-1 (Tg(Gasp-1)) present an increase of muscle mass but develop metabolic disorders with aging. Here, we showed that overexpression of Gasp-2 increases the muscular mass without metabolic defects. We also found that Tg(Gasp-2) mice displayed, like Mstn-/- mice, a switch from slow- to fast-twitch myofibers whereas Tg(Gasp-1) mice exhibit a reverse switch. Our studies supported the fact that GASP-2 has less affinity than GASP-1 for Mstn, leading to a constitutive Mstn upregulation only in Tg(Gasp-1) mice, responsible for the observed phenotypic differences. Altogether, our findings highlighted a gene expression regulatory network of TGF-ß members and their inhibitors in muscle.

Assessing patterns of genetic admixture between sheep breeds: Case study in Algeria.

In developing countries, cross-breeding between local breeds and indigene or exotic breeds represents one of the main threats to the livestock diversity, leading to genetic dilution and loss of unique allelic combination underlying essential local adaptive traits. In this study, two Algerian sheep breeds, known to be highly admixed, were considered as a case study, to demonstrate how combination of different methodologies coupled with the use of specific softwares can be efficient to assess the spatial structuration of a hybrid zone, even in a case of extreme admixture. A fine sampling covering distribution areas of both breeds was implemented in order to study the admixture area and adjacent zones from a phenotypic (i.e., 19 quantitative traits were considered) and a genetic point of view (i.e., 21 microsatellites markers were used). Both approaches gave concordant patterns, highlighting areas with sheep most differentiated (or less admixed) for each breed. In detail, the region of Biskra appeared as the most preserved for the Ouled-Djellal breed and the northwest of Laghouat was identified as the most preserved area for the Rembi breed. The approach proposed in the study offers a low-cost solution to identify the most representative flocks of a breed, allowing the implementation of efficient conservation plans.

Expression of SERPINA3s in cattle: focus on bovSERPINA3-7 reveals specific involvement in skeletal muscle.

α1-Antichymotrypsin is encoded by the unique SERPINA3 gene in humans, while it is encoded by a cluster of eight closely related genes in cattle. BovSERPINA3 proteins present a high degree of similarity and significant divergences in the reactive centre loop (RCL) domains which are responsible for the antiprotease activity. In this study, we analysed their expression patterns in a range of cattle tissues. Even if their expression is ubiquitous, we showed that the expression levels of each serpin vary in different tissues of 15-month-old Charolais bulls. Our results led us to focus on bovSERPINA3-7, one of the two most divergent members of the bovSERPINA3 family. Expression analyses showed that bovSERPINA3-7 protein presents different tissue-specific patterns with diverse degrees of N-glycosylation. Using a specific antibody raised against bovSERPINA3-7, Western blot analysis revealed a specific 96 kDa band in skeletal muscle. BovSERPINA3-7 immunoprecipitation and mass spectrometry revealed that this 96 kDa band corresponds to a complex of bovSERPINA3-7 and creatine kinase M-type. Finally, we reported that the bovSERPINA3-7 protein is present in slow-twitch skeletal myofibres. Precisely, bovSERPINA3-7 specifically colocalized with myomesin at the M-band region of sarcomeres where it could interact with other components such as creatine kinase M-type. This study opens new prospects on the bovSERPINA3-7 function in skeletal muscle and promotes opportunities for further understanding of the physiological role(s) of serpins.