Genetically modified non-human mammals and cells

Abstract

Genetically modified mammals are described which lack the mannan binding lectin associated serine protease MASP-2, together with methods and constructs for their production. Such mammals are useful as models for disorders of the complement system, and in the identification of treatments for such disorders. Also described are mammals which lack the associated protein MAp19; such mammals may also lack MASP-2.

1 . A method for production of an antibody directed against a human MASP-2 and/or human MAp19 protein produced by an exogenous human gene in a genetically modified rodent, wherein the gene encoding endogenous MASP-2 polypeptide and/or the gene encoding endogenous MAp19 polypeptide is/are absent or partially absent or disrupted. 
     
     
         2 . The method of  claim 1 , wherein the genetically modified rodent is a mouse. 
     
     
         3 . The method of  claim 1 , wherein all the endogenous MASP-2 and/or endogenous MAp19 gene sequences are absent from the genome. 
     
     
         4 . The method of  claim 1 , wherein exons 10, 11, and 12 of the endogenous MASP-2 gene have been deleted from the genome of the genetically modified rodent. 
     
     
         5 . The method of  claim 1 , wherein exon 5 of the endogenous MASP-2 gene has been deleted from the genome of the genetically modified rodent. 
     
     
         6 . The method of  claim 1 , wherein the human MASP-2 protein is produced by an exogenous gene encoding human MASP-2. 
     
     
         7 . The method of  claim 1 , wherein the human MAp19 protein is produced by an exogenous gene encoding human MAp19.