Modelling haematopoietic malignancies in the mouse and therapeutical implications.
Modelling human disease in the mouse has become an essential activity in biomedical research in order to unravel molecular mechanisms underlying pathological conditions as well as to determine in vivo the consequences of aberrant gene function. The mouse is by far the most accessible mammalian system physiologically similar to humans. Furthermore, the development of novel techniques for manipulating the murine genome, which allow the in vivo modification of virtually any genomic region in a time and/or tissue specific manner, renders the mouse an ideal model system to study human pathological conditions. Modelling human diseases in mice has reached an even greater relevance in the field of haematological malignancies, due to the already advanced characterization of the molecular basis of many haematological disorders. In this review, we describe the most important technological developments that made it possible to reproduce in the mouse the genetic lesions that characterize human haematological malignancies, thus often generating faithful mouse models of the human condition. We provide specific examples of the advantages and limitations of the various genetic approaches utilized to model leukaemia and lymphoma in the mouse. Finally, we discuss the power of mouse modelling in developing and testing novel therapeutic modalities in pre-clinical studies.
Bernardi
Rosa
R
Molecular Biology Program and Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, Graduate School of Medical Sciences, Cornell University, 1275 York Avenue, New York, NY 10021, USA.
Grisendi
Silvia
S
Pandolfi
Pier Paolo
PP
D000818:Animals; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013752:Tetracycline / Q000494:pharmacology
D016044:Fusion Proteins, bcr-abl; D013752:Tetracycline