SRF, un facteur de transcription crucial dans la physiologie des muscles squelettiques (Contribution au vieillissement et à l'hypertrophie)

Afin de déterminer le rôle de SRF dans la physiologie du muscle adulte, nous avons créé un modèle murin d'invalidation inductible de SRF dans les muscles squelettiques. Après induction de la perte de SRF, les muscles mutants présentent des altérations similaires à celles observées lors du vieillissement musculaire. L'expression de SRF diminuant de façon drastique avec le temps dans des muscles contrôles, cette perte de SRF avec l'âge pourrait contribuer au processus naturel du vieillissement. Afin d'évaluer le rôle de SRF dans l'hypertrophie, j'ai soumis les muscles de souris contrôles et mutantes à une surcharge et montré que seuls les muscles contrôles présentent une réponse hypertrophique. Ce défaut d'hypertrophie dans les muscles mutants est due à une altération de la prolifération et de la fusion des cellules satellites, SRF contrôlant de façon paracrine l'expression de IL6 et IL4. Nos résultats montrent que SRF est impliqué dans le maintien et l'hypertrophie musculaire.To investigate SRF function in adult skeletal muscle physiology, we developed a myofiber-specific and tamoxifen-inducibie SRF Knockout mice model. After induction of SRF loss, mutant muscles exhibits similar alterations to those observed during muscle aging. We also observed an important age-associated decrease in SRF expression in control muscles. Thus SRF loss with age could contribute to the natural muscle aging process. To assess the role of SRF during hypertrophy, I submitted muscles of mutant and control mice to an overload-induced hypertrophy and showed that only controls muscles show a hypertrophic response. The lack of hypertrophy in mutant muscles is due to an impairment of satellite cells proliferation and fusion. In fact, SRF enhance hypertrophy through the control of IL6 and IL4 expression in a paracrine fashion. Our results show that SRF is involved in skeletal muscle maintenance and hypertrophy.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Rôle du facteur de transciption SRF (Serum Response Factor) dans le coeur adulte et les muscles squelettiques chez la souris

PARIS5-BU-Necker : Fermée (751152101) / SudocSudocFranceF

Caractérisation de modèles animaux pour l' étude des différents types de motoneurones

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Biomedical research: incidental and unexpected findings. Classification and management

Note from the Ethics committee. "Incidental and Unexpected Research Findings" Group. Coordinator: François Eisinge

Testis hormone-sensitive lipase expression in spermatids is governed by a short promoter in transgenic mice

A testicular form of hormone-sensitive lipase (HSLtes), a triacylglycerol lipase, and cholesterol esterase, is expressed in male germ cells. Northern blot analysis showed HSLtes mRNA expression in early spermatids. Immunolocalization of the protein in human and rodent seminiferous tubules indicated that the highest level of expression occurred in elongated spermatids. We have previously shown that 0.5 kilobase pairs of the human HSLtes promoter directs testis-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice and determined regions binding nuclear proteins expressed in testis but not in liver (Blaise, R,, Grober, J,, Rouet, P., Tavernier, G., Daegelen, D., and Langin, D. (1999) J. Biol. Chem. 274, 9327-9334). Mutation of a SRY/Sox-binding site in one of the regions did not impair in vivo testis-specific expression of the reporter gene. Further transgenic analyses established that 95 base pairs upstream of the transcription start site were sufficient for correct testis expression. In gel retardation assays using early spermatid nuclear extracts, a germ cell-specific DNA-protein interaction was mapped between -46 and -29 base pairs. The DNA binding nuclear protein showed properties of zinc finger transcription factors. Mutation of the region abolished reporter gene activity in transgenic mice, showing that it is necessary for testis expression of HSLtes

Effects of anabolic/androgenic steroids on regenerating skeletal muscles in the rat

International audienceWe have examined the effect of male sexual hormones on the regeneration of skeletal muscles. Degeneration/regeneration of the left soleus and extensor digitorum longus muscles (EDL) of Wistar male rats was induced by an injection of snake venom (2 μg, Notechis scutatus scutatus ). During the muscle regeneration (25 days), rats were treated with either oil (CON), nandrolone (NAN), NAN combined with exercise (NAN + EXE) or were castrated (CAS). Muscle growth and myosin heavy chain (MyHC) isoform content of regenerating muscles were studied. Castration altered the concentrations of MyHC in venom‐treated EDL ( P  0.05). In conclusion, it is possible that male sexual hormones play a role in the growth (synthesis of contractile proteins) of regenerating muscles in rat. In addition, contrary to NAN + EXE, NAN could be beneficial to soleus regeneration