Recent advances in the manipulation of murine gene expression and its utility for the study of human neurological disease

Cazzin, Chiara and Ring, Christopher J. ORCID: https://orcid.org/0000-0002-9278-0942 (2010) Recent advances in the manipulation of murine gene expression and its utility for the study of human neurological disease. B B A - Molecular Basis of Disease, 1802 (10) . pp. 796-807. ISSN 0925-4439 [Article] (doi:10.1016/j.bbadis.2009.11.005)

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Abstract

Transgenic mouse models have vastly contributed to our
knowledge of the genetic and molecular pathways underlying the pathogenesis of neurological disorders that affect millions of people worldwide. Not only they have allow the generation of disease models mimicking the human pathological state but they have also permit the exploration of the pathological role of specific genes through the generation of knock-out and knock-in models. Classical constitutive transgenic mice have several limitations however, due to behavioral adaptation process occurring and conditional mouse models are time-consuming and often lack of extensive spatial ortemporal control of gene manipulation. These limitations could be overcome by means of innovative methods that are now available such as RNAi, viral vectors and large cloning DNA vectors. These tools have been extensively used for the generation of mouse models and are characterized by the superior control of transgene expression that has proved invaluable in the assessment of novel treatments for neurological diseases and to further investigate the molecular processes underlying the etiopathology of neurological disorders. Furthermore, in association with classical transgenic mouse models, they have allowed the validation of innovative therapeutic strategies for the treatment of human neurological disorders. This review describes how these tools have overcome the limitations of classical transgenic mouse models and how they have been of value for the study of human neurological diseases.

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