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Using Genetically Engineered Mouse Models to Understand Low-Grade Glioma Development and Growth in Children

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Animal Models of Brain Tumors

Part of the book series: Neuromethods ((NM,volume 77))

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Abstract

Pilocytic astrocytoma (PA) is the most common brain tumor observed in children. These tumors can form sporadically in children with no underlying genetic disease or in 15–20% of children with neurofibromatosis type 1 (NF1), an inherited cancer predisposition syndrome. Though similar histologically, the genetic basis for PA formation in these two populations are distinct. In the general population, PAs likely arise in response to aberrant BRAF activation, whereas in the context of NF1, they result from bi-allelic inactivation of the NF1 tumor suppressor gene. Since accurate rodent models of sporadic PA are currently under development, Nf1 genetically engineered mouse models have served as tractable systems to study the role of aberrant intracellular signaling, nonneoplastic cells in the tumor microenvironment, and genomic modifiers on gliomagenesis. These small-animal models have also been used as platforms to discover next-generation targeted therapies and to evaluate the efficacy of these potential anticancer treatments prior to clinical trials for NF1-associated astrocytomas.

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Acknowledgments

We thank Dr. Sonika Dahiya and Mr. Scott Gianino for the images of human pilocytic astrocytoma specimens and mouse Nf1 optic gliomas, respectively. Ibrahim Hussain is supported by funding from the Doris Duke Charitable Foundation to Washington University School of Medicine. David H. Gutmann is supported by funding from the National Cancer Institute, the National Institutes of Health, the James S. McDonnell Foundation, and the Department of Defense.

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  1. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

    Aparna Kaul, Ibrahim Hussain & David H. Gutmann

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  1. Aparna Kaul
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  2. Ibrahim Hussain
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  3. David H. Gutmann
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Correspondence to David H. Gutmann .

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Editors and Affiliations

  1. Instituto Cajal, Molecular, Cellular & Developmental Neur, CSIC, Avda. Doctor Arce 37, Madrid, 28002, Spain

    Ricardo Martínez Murillo

  2. de la Rioja (CIBIR), Oncology Area, Centro de Investigación Biomédica, C/ Piqueras 98, Logroño, 26006, Spain

    Alfredo Martínez

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Kaul, A., Hussain, I., Gutmann, D.H. (2012). Using Genetically Engineered Mouse Models to Understand Low-Grade Glioma Development and Growth in Children. In: Martínez Murillo, R., Martínez, A. (eds) Animal Models of Brain Tumors. Neuromethods, vol 77. Humana Press, Totowa, NJ. https://doi.org/10.1007/7657_2011_29

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  • DOI: https://doi.org/10.1007/7657_2011_29

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