Nonhuman model animal lacking the ability to control...

Details Nonhuman model animal lacking the ability to control... Nonhuman model animal lacking the ability to control...

A - Human Necessities

01

K

A01K 67/027 (2006.01) C07K 14/47 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2471432

It is intended to provide a model animal which is useful in identifying a molecule specifically controlling the mobility of lymphocytes and thus clarifying the pathogenic conditions at the molecular level of immunological diseases such as allergy, autoimmune diseases, GvH and graft rejection, or developing a novel therapy. A model animal such as a DOCK2 knockout mouse, in which the function of controlling lymphocyte migration has been deleted or regulated, is constructed by deleting DOCK2 gene on chromosome. In this DOCK2 knockout mouse, the function of activating Rac to thereby promote the reconstruction of actin cell skeleton, the lymphocyte migration function due to the stimuli with chemokines such as SLC, SDF-1 and BLC, the homing function toward secondary lymph tissues such as spleen, lymph nodes and Peyer~s patch and the function of releasing matured thymus T cells into peripheral blood are injured and, as a result, immune responses are regulated.

L'invention concerne un modèle animal pouvant être utilisé pour l'identification d'une molécule régulant spécifiquement la mobilité des lymphocytes et ainsi pour clarifier les état pathogènes, au niveau moléculaire, de maladies immunologiques telles que les allergies, les maladies autoimmunes, la réaction du greffon contre l'hôte et le rejet du greffon, ou bien pour développer une nouvelle thérapie. Un modèle animal tel qu'une souris knockout DOCK2, chez laquelle la fonction de régulation de la migration des lymphocytes a été supprimée ou régulée, est construit par délétion du gène DOCK2 sur le chromosome. Dans cette souris knockout DOCK2, la fonction d'activation de Rac pour ainsi stimuler la reconstruction du squelette d'actine cellulaire, la fonction de migration des lymphocytes due.aux stimuli avec des chimiokines telles que SLC, SDF-1 et BLC, la fonction de homing vers des tissus lymphatiques secondaires tels que la rate, les ganglions lymphatiques et les plaques de Peyer et la fonction de libération des lymphocytes T du thymus mûrs dans le sang périphérique sont altérées et, en conséquence, les réponses immunitaires sont régulées.

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