Mice as Experimental Organisms

Abstract

The mouse is extensively used as a model system to reproduce human diseases in a mammalian system, and to consequently allow to examine the molecular and pathogenic features of the disease in a context that is as close as possible to the human being. The use of the mouse has been particularly useful in three large areas of experimental pathogenesis: (1) classic monogenic diseases, (2) cancer development and progression and (3) developmental genetics and congenital pathologies. In each of these areas, significant progress has been made in recent years. Here, after a short introduction to the biology of the mouse and its history as a model organism, we summarise the current status of genetic manipulation of the mouse genome, provide an overview of current knowledge and illustrate some recent advancements.

Key Concepts:

  • The mouse is a model of choice to study human disease because is relatively easy to handle while being surprisingly similar to humans.

  • The mouse and human genomes share considerable homology.

  • The pluripotency of early embryonic cells is the basis of the possibility to manipulate the mouse genome and obtain animals carrying specific mutations.

  • Current methodology consent to modify the mouse genome in several ways, including conventional, dynamic and inducible mutations.

  • Mouse models of human genetic diseases provide an ideal basis for studying the pathogenic mechanism and testing innovative therapies.

  • Key concept in cancer initiation and progression have been established thanks to mouse models.

  • Experimentally, we can use the mouse to visualise complex processes (cell communication, differentiation fate and embryonic development) in a mammalian system.

  • Embryonic development of Vertebrates is highly conserved, reflecting extensive genome conservation.

  • Pluripotency is also achieved by reprogramming of somatic cells; this has great implication for biology of stem cells and possible innovative therapies.

Keywords: mice; breeding; genetics; development; disease; mammals

Figure 1.

Manipulating the mouse genome: where, when and why. A scheme to summarise the three principal genetic manipulation and the phenotypic studies that are most commonly performed, in relation with developmental and post‐natal stages of the mouse. On the left, a photographic description of the various embryonic stages considered. On the right, the manipulations required to generate the different models and the modified strains that can be obtained: (a) injection of foreign DNA to generate transgenic models, reproduced from Dr. Hirsch, University of Torino, (b) injection of modified ES cells to generate knock‐out and conditional models, reproduced from Dr. Hirsch, University of Torino and (c, d) cross‐breeding with Cre‐expressing animals to carry out somatic cell genetics. For each of these strategies, a short list of common research applications is reported.

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Merlo, Giorgio, Altruda, Fiorella, and Poli, Valeria(May 2012) Mice as Experimental Organisms. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002029.pub2]