AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis

Myotubular myopathy (XLMTM, OMIM 310400) is a severe congenital muscular disease due to mutations in the myotubularin gene (MTM1) and characterized by the presence of small myofibers with frequent occurrence of central nuclei. Myotubularin is a ubiquitously expressed phosphoinositide phosphatase with a muscle-specific role in man and mouse that is poorly understood. No specific treatment exists to date for patients with myotubular myopathy. We have constructed an adeno-associated virus (AAV) vector expressing myotubularin in order to test its therapeutic potential in a XLMTM mouse model. We show that a single intramuscular injection of this vector in symptomatic Mtm1-deficient mice ameliorates the pathological phenotype in the targeted muscle. Myotubularin replacement in mice largely corrects nuclei and mitochondria positioning in myofibers and leads to a strong increase in muscle volume and recovery of the contractile force. In addition, we used this AAV vector to overexpress myotubularin in wild-type skeletal muscle and get insight into its localization and function. We show that a substantial proportion of myotubularin associates with the sarcolemma and I band, including triads. Myotubularin overexpression in muscle induces the accumulation of packed membrane saccules and presence of vacuoles that contain markers of sarcolemma and T-tubules, suggesting that myotubularin is involved in plasma membrane homeostasis of myofibers. This study provides a proof-of-principle that local delivery of an AAV vector expressing myotubularin can improve the motor capacities of XLMTM muscle and represents a novel approach to study myotubularin function in skeletal muscle

Conférence de Mme Anne-Marie Blondeau

Blondeau Anne-Marie. Conférence de Mme Anne-Marie Blondeau. In: École pratique des hautes études, Section des sciences religieuses. Annuaire. Tome 92, 1983-1984. 1983. pp. 133-138

Conférence de Mme Anne-Marie Blondeau

Blondeau Anne-Marie. Conférence de Mme Anne-Marie Blondeau. In: École pratique des hautes études, Section des sciences religieuses. Annuaire. Tome 98, 1989-1990. 1989. pp. 110-116

Conférence de Mme Anne-Marie Blondeau

Blondeau Anne-Marie. Conférence de Mme Anne-Marie Blondeau. In: École pratique des hautes études, Section des sciences religieuses. Annuaire. Tome 99, 1990-1991. 1990. pp. 69-74

R. A. Paul, The Tibetan Symbolic World. Psychoanalytic Explorations

Blondeau Anne-Marie. R. A. Paul, The Tibetan Symbolic World. Psychoanalytic Explorations. In: L'Homme, 1983, tome 23 n°2. pp. 141-143

Conférence de Mme Anne-Marie Blondeau

Blondeau Anne-Marie. Conférence de Mme Anne-Marie Blondeau. In: École pratique des hautes études, Section des sciences religieuses. Annuaire. Tome 100, 1991-1992. 1991. pp. 85-89

Conférence de Mme Anne-Marie Blondeau

Blondeau Anne-Marie. Conférence de Mme Anne-Marie Blondeau. In: École pratique des hautes études, Section des sciences religieuses. Annuaire. Tome 101, 1992-1993. 1992. pp. 67-72

Conférence de Mme Anne-Marie Blondeau

Blondeau Anne-Marie. Conférence de Mme Anne-Marie Blondeau. In: École pratique des hautes études, Section des sciences religieuses. Annuaire. Tome 110, 2001-2002. 2001. pp. 105-107

La Vie de l'enfant Padma 'od-'bar : du texte à l'image

The Life of the Child Padma 'od-'bar : from the text to the painted image. The play, the Life of the Child Padma 'od-'bar is very popular amongst the Tibetan people. Apart from the " libretti ", proper to each theatrical company, several written versions have been published, though these come down to two main ones, the first published in Kalimpong in 1959, and the second in Lhasa in 1982. Furthermore, the same narrative is related by the itinerant storytellers, the mani-pas, who illustrate their story by showing details from the scenes of a thangka. A comparison between four of these paintings shows that, beyond stylistic differences, a large homogeneity exists in their composition. One may wonder whether this homogeneity is the result of a common geographical origin, which may link them to a school from Khams. Putting the texts and paintings side by side, it becomes clear that — apart from a few details — all the scenes in the paintings faithfully follow the texts. Nevertheless, it is necessary to combine both written versions in order to get a complete " reading " of the thangkas. This fact suggests that the two modern versions are incomplete, and that it would be useful to find a more ancient text. Thus we have a further example of « narrative » painting very precisely linked to a text. Yet, contrary to other such paintings, previously studied, those illustrating the life of Padma 'od-'bar lack strictness in their composition, since the progress of the story sometimes requires the reader to jump in disorder from one place to another. If one adds the naive technique used in three out of four of these thangkas, one may ask whether this might not be considered as a criterion for identifying the paintings used by the mani-pas. Finally, this example, following others, prompts one to look to literary sources as the probable origin of the so-called " narrative " paintings.Blondeau Anne-Marie. La Vie de l'enfant Padma 'od-'bar : du texte à l'image. In: Arts asiatiques, tome 43, 1988. pp. 40-59

Tibetan Medical paintings. Illustrations to the Blue Beryl treatise of Sangye Gyamtso (1653-1705)

Blondeau Anne-Marie. Tibetan Medical paintings. Illustrations to the Blue Beryl treatise of Sangye Gyamtso (1653-1705). In: Arts asiatiques, tome 48, 1993. pp. 168-169