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Modeling RASopathies with Genetically Modified Mouse Models

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Book cover ERK Signaling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1487))

Abstract

The RAS/MAPK signaling pathway plays key roles in development, cell survival and proliferation, as well as in cancer pathogenesis. Molecular genetic studies have identified a group of developmental syndromes, the RASopathies, caused by germ line mutations in this pathway. The syndromes included within this classification are neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NS-ML, formerly known as LEOPARD syndrome), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS, NF1-like syndrome), capillary malformation–arteriovenous malformation syndrome (CM-AVM), and hereditary gingival fibromatosis (HGF) type 1. Although these syndromes present specific molecular alterations, they are characterized by a large spectrum of functional and morphological abnormalities, which include heart defects, short stature, neurocognitive impairment, craniofacial malformations, and, in some cases, cancer predisposition. The development of genetically modified animals, such as mice (Mus musculus), flies (Drosophila melanogaster), and zebrafish (Danio rerio), has been instrumental in elucidating the molecular and cellular bases of these syndromes. Moreover, these models can also be used to determine tumor predisposition, the impact of different genetic backgrounds on the variable phenotypes found among the patients and to evaluate preventative and therapeutic strategies. Here, we review a wide range of genetically modified mouse models used in the study of RASopathies and the potential application of novel technologies, which hopefully will help us resolve open questions in the field.

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Acknowledgements

We thank to Dr. Raquel García-Medina for the critical reading of this manuscript. Work was supported by grants from Fondo de Investigación Sanitaria (PI042124, PI08-1623, PI11-02529), Autonomous Community of Madrid (GR/SAL/0349/2004), and Fundación Ramón Areces (FRA 01-09-001) to C.G. I.H.-P. was supported by PFIS grant from the Instituto de Salud Carlos III.

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  1. Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain

    Isabel Hernández-Porras & Carmen Guerra

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  1. Isabel Hernández-Porras
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  2. Carmen Guerra
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Correspondence to Carmen Guerra .

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  1. Institut de Biologia Molecular de Barcelona-CSIC, Parc Científic de Barcelona, Barcelona, Spain

    Gerardo Jimenez

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Hernández-Porras, I., Guerra, C. (2017). Modeling RASopathies with Genetically Modified Mouse Models. In: Jimenez, G. (eds) ERK Signaling. Methods in Molecular Biology, vol 1487. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6424-6_28

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  • DOI: https://doi.org/10.1007/978-1-4939-6424-6_28

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