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1.
J Neurosci ; 32(37): 12885-95, 2012 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-22973012

RESUMEN

Live imaging studies of the processes of demyelination and remyelination have so far been technically limited in mammals. We have thus generated a Xenopus laevis transgenic line allowing live imaging and conditional ablation of myelinating oligodendrocytes throughout the CNS. In these transgenic pMBP-eGFP-NTR tadpoles the myelin basic protein (MBP) regulatory sequences, specific to mature oligodendrocytes, are used to drive expression of an eGFP (enhanced green fluorescent protein) reporter fused to the Escherichia coli nitroreductase (NTR) selection enzyme. This enzyme converts the innocuous prodrug metronidazole (MTZ) to a cytotoxin. Using two-photon imaging in vivo, we show that pMBP-eGFP-NTR tadpoles display a graded oligodendrocyte ablation in response to MTZ, which depends on the exposure time to MTZ. MTZ-induced cell death was restricted to oligodendrocytes, without detectable axonal damage. After cessation of MTZ treatment, remyelination proceeded spontaneously, but was strongly accelerated by retinoic acid. Altogether, these features establish the Xenopus pMBP-eGFP-NTR line as a novel in vivo model for the study of demyelination/remyelination processes and for large-scale screens of therapeutic agents promoting myelin repair.


Asunto(s)
Enfermedades Desmielinizantes/patología , Enfermedades Desmielinizantes/fisiopatología , Modelos Animales de Enfermedad , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Regeneración Nerviosa/fisiología , Xenopus laevis/anatomía & histología , Xenopus laevis/fisiología , Animales , Humanos
2.
Neurogenetics ; 11(1): 27-40, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19517146

RESUMEN

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy. The loss of function of the smn1 gene, the main supplier of survival motor neuron protein (SMN) protein in human, leads to reduced levels of SMN and eventually to SMA. Here, we ask if the amphibian Xenopus tropicalis can be a good model system to study SMA. Inhibition of the production of SMN using antisense morpholinos leads to caudal muscular atrophy in tadpoles. Of note, early developmental patterning of muscles and motor neurons is unaffected in this system as well as acetylcholine receptors clustering. Muscular atrophy seems to rather result from aberrant pathfinding and growth arrest and/or shortening of motor axons. This event occurs in the absence of neuronal cell bodies apoptosis, a process comparable to that of amyotrophic lateral sclerosis. Xenopus tropicalis is revealed as a complementary animal model for the study of SMA.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Atrofia Muscular Espinal/genética , Proteína 1 para la Supervivencia de la Neurona Motora/biosíntesis , Secuencia de Aminoácidos , Animales , Apoptosis , Secuencia de Bases , Modelos Animales de Enfermedad , Humanos , Hibridación in Situ , Datos de Secuencia Molecular , Oligonucleótidos Antisentido/farmacología , Receptores Colinérgicos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Xenopus
3.
Differentiation ; 74(5): 244-53, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16759290

RESUMEN

Survivin is a member of the inhibitor of apoptosis proteins (IAP) family. These proteins contain one to three zinc-binding motifs termed bacculoviral IAP-binding repeats (BIRs). Survivin contains a single BIR motif. Contrary to other members that directly interact with caspases and inhibit apoptosis, Survivin is believed to have both antiapoptotic and proliferative functions. In mammals, Survivin is not detected in most adult tissues except in endothelial cells of newly formed capillaries and large blood vessels. Importantly, Survivin is highly expressed in all common human cancers. To gain a better view of Survivin expression and function during development, we used the amphibian Xenopus developmental model. We show that the genomes of X. laevis, X. tropicalis, Zebrafish, fugu pufferfish, and rainbow trout encode two different Survivin genes (Su1 and Su2), contrary to mammalian genomes, which encode a single one. In X. laevis, these two genes have a differential spatiotemporal transcription pattern. Transgenic expression of Su1 leads to an enlargement of tadpole's blood vessels with an increase in the number of endothelial cells. This effect requires a functional BIR domain and the p34/cdc2 phosphorylation site. It does not seem to rely on the antiapoptotic activity of Su1 as it is not observed in tadpoles overexpressing other antiapoptotic factors such as XIAP or BclXL. We conclude that Su1 ubiquitous gain of function leads directly or indirectly to an increase in blood vessels size via the proliferation of endothelial cells.


Asunto(s)
Vasos Sanguíneos/embriología , Proteínas Inhibidoras de la Apoptosis/metabolismo , Secuencia de Aminoácidos , Animales , Regulación del Desarrollo de la Expresión Génica , Genoma , Humanos , Hibridación in Situ , Proteínas Inhibidoras de la Apoptosis/química , Proteínas Inhibidoras de la Apoptosis/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Xenopus
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