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Manzini, Maria Chiara

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Manzini

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Maria Chiara

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Manzini, Maria Chiara
Author's Publications: search.filters.isAuthorOfPublication.232fe4ab-95c5-4c50-b82d-228d531e45c0

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    A Splice Site Mutation in Laminin-α2 Results in a Severe Muscular Dystrophy and Growth Abnormalities in Zebrafish
    (Public Library of Science, 2012) Gupta, Vandana; Kawahara, Genri; Myers, Jennifer A.; Chen, Aye T.; Hall, Thomas E.; Manzini, Maria Chiara; Currie, Peter D.; Zhou, Yi; Zon, Leonard; Kunkel, Louis; Beggs, Alan
    Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of inherited muscle disorders. In patients, muscle weakness is usually present at or shortly after birth and is progressive in nature. Merosin deficient congenital muscular dystrophy (MDC1A) is a form of CMD caused by a defect in the laminin-α2 gene (LAMA2). Laminin-α2 is an extracellular matrix protein that interacts with the dystrophin-dystroglycan (DGC) complex in membranes providing stability to muscle fibers. In an N-ethyl-N-nitrosourea mutagenesis screen to develop zebrafish models of neuromuscular diseases, we identified a mutant fish that exhibits severe muscular dystrophy early in development. Genetic mapping identified a splice site mutation in the lama2 gene. This splice site is highly conserved in humans and this mutation results in mis-splicing of RNA and a loss of protein function. Homozygous lama2 mutant zebrafish, designated lama2cl501/cl501, exhibited reduced motor function and progressive degeneration of skeletal muscles and died at 8–15 days post fertilization. The skeletal muscles exhibited damaged myosepta and detachment of myofibers in the affected fish. Laminin-α2 deficiency also resulted in growth defects in the brain and eye of the mutant fish. This laminin-α2 deficient mutant fish represents a novel disease model to develop therapies for modulating splicing defects in congenital muscular dystrophies and to restore the muscle function in human patients with CMD.
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    Isolation and Culture of Post-Natal Mouse Cerebellar Granule Neuron Progenitor Cells and Neurons
    (Journal of Visualized Experiments, 2009) Lee, Hae Young; Greene, Lloyd A.; Mason, Carol A.; Manzini, Maria Chiara
    The cerebellar cortex is a well described structure that provides unique opportunities for studying neuronal properties and development. Of the cerebellar neuronal types (granule cells, Purkinje cells and inhibitory interneurons), granule neurons are by far the most numerous and are the most abundant type of neurons in the mammalian brain. In rodents, cerebellar granule neurons are generated during the first two post-natal weeks from progenitor cells in the outermost layer of the cerebellar cortex, the external granule layer (EGL). The protocol presented here describes techniques to enrich and culture granule neurons and their progenitor cells from post-natal mouse cerebellum. We will describe procedures to obtain cultures of increasing purity, which can be used to study the differentiation of proliferating progenitor cells into granule neurons. Once the progenitor cells differentiate, the cultures also provide a homogenous population of granule neurons for experimental manipulation and characterization of phenomena such as synaptogenesis, glutamate receptor function, interaction with other purified cerebellar cells or cell death.