Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene.
Grobet, Luc ; Pirottin, Dimitri ; Farnir, Frédéric et al
in Genesis (New York, N.Y. : 2000) (2003), 35(4), 227-38
By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular ... [more ▼]
By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular hypertrophy of the same magnitude as that observed for constitutive myostatin knockout mice. This formally demonstrates that striated muscle is the production site of functional myostatin and that this member of the TGFbeta family of growth and differentiation factors regulates muscle mass not only during early embryogenesis but throughout development. It indicates that myostatin antagonist could be used to treat muscle wasting and to promote muscle growth in man and animals. [less ▲]Detailed reference viewed: 46 (11 ULg)
Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice.
; ; et al
in Molecular & Cellular Biology (2002), 22(22), 8005-14
Members of the heat shock factor (HSF) family are evolutionarily conserved regulators that share a highly homologous DNA-binding domain. In mammals, HSF1 is the main factor controlling the stress ... [more ▼]
Members of the heat shock factor (HSF) family are evolutionarily conserved regulators that share a highly homologous DNA-binding domain. In mammals, HSF1 is the main factor controlling the stress-inducible expression of Hsp genes while the functions of HSF2 and HSF4 are less clear. Based on its developmental profile of expression, it was hypothesized that HSF2 may play an essential role in brain and heart development, spermatogenesis, and erythroid differentiation. To directly assess this hypothesis and better understand the underlying mechanisms that require HSF2, we generated Hsf2 knockout mice. Here, we report that Hsf2(-/-) mice are viable and fertile and exhibit normal life span and behavioral functions. We conclude that HSF2, most probably because its physiological roles are integrated into a redundant network of gene regulation and function, is dispensable for normal development, fertility, and postnatal psychomotor function. [less ▲]Detailed reference viewed: 20 (4 ULg)
Differential heat shock gene hsp70-1 response to toxicants revealed by in vivo study of lungs in transgenic mice
; ; Munaut, Carine et al
in Cell Stress & Chaperones (2002), 7(4), 387-395
Members of heat shock proteins (Hsp70) family have been considered to respond to a large variety of stressful conditions. But it was suggested that, in pulmonary cells, Hsp response depends more closely ... [more ▼]
Members of heat shock proteins (Hsp70) family have been considered to respond to a large variety of stressful conditions. But it was suggested that, in pulmonary cells, Hsp response depends more closely on the type of stimulus. The lungs are critical organs potentially subjected to air pollution affecting respiratory function and, therefore, these organs are of particular interest with regard to the stress response. To investigate the stress dependence of Hsp70 response in lungs, we created transgenic mice where the firefly luciferase reporter gene is under the control of the murine hsp70-1 promoter and exposed them to different sublethal toxic conditions. For each condition, the level of transgene induction and pulmonary toxicity were assessed. We found that hsp70-1 promoter was stimulated by heat shock and Cadmium but not by ozone, paraquat, and parathion, even if these chemicals induced respiratory distress and lung inflammation. Similar observations were made when expression of the endogenous hsp70-1 gene was analyzed, indicating that our transgenic model was accurately detecting hsp70-1 induction. Thereby, it appeared that hsp70-1 response is selective and depends on signaling pathways triggered by the toxicants rather than by their pathologic toxicity per se. Furthermore, because all the chemicals used in our study have been previously described to increase the level of oxidative stress, it indicates that there is no direct and simple correlation between hsp70-1 response and the level of oxidative stress, but more specific oxidative patterns should be involved in Hsp regulation. [less ▲]Detailed reference viewed: 25 (5 ULg)