Human artificial chromosome containing human antibody lambda light chain gene and non-human animal containing the human artificial chromosome capable of genetic transmission

Abstract

The present invention relates to a human artificial chromosome which is genetically transmissible to the next generation with high efficiency and the method for using the same. More specifically, the present invention relates to: a human artificial chromosome in which an about 3.5 Mb to about 1 Mb region containing an antibody λ light chain gene derived from human chromosome 22 is bound to a chromosome fragment which is transmissible to a progeny through a germ line of a non-human animal, said chromosome fragment is derived from another human chromosome; a non-human animal carrying the human artificial chromosome and an offspring thereof; a method for producing the non-human animal; a method for producing a human antibody using the nonhuman animal or an offspring thereof; and a human antibody-producing mouse carrying the human artificial chromosome.

What is claimed: 
     
         1 . A human antibody-producing mouse, wherein an unrearranged human antibody heavy chain locus, an unrearranged human antibody κ light chain locus, and an unrearranged human antibody λ light chain locus are carried, at least both alleles of endogenous antibody heavy chain and κ light chain are disrupted or inactivated, and a human antibody heavy chain comprising a human antibody Ig γ isotype, a human antibody κ light chain, and a human antibody λ light chain are expressed in serum. 
     
     
         2 . The human antibody-producing mouse of  claim 1 , which carries at least 40% of the variable region of the human antibody κ light chain. 
     
     
         3 . The human antibody-producing mouse of  claim 1 , which carries all the variable regions of the human antibody heavy chain, the human antibody κ light chain, and the human antibody λ light chain. 
     
     
         4 . The human antibody-producing mouse of  claim 1 , wherein a human antibody heavy chain locus, a human antibody κ light chain locus, and a human antibody λ locus are retained on a chromosome fragment derived from a human. 
     
     
         5 . The human antibody-producing mouse of  claim 1 , wherein the human antibody heavy chain locus and the human antibody λ light chain locus are retained on ΔHAC or ΔΔHAC. 
     
     
         6 . The human antibody-producing mouse of  claim 1 , wherein the human antibody κ light chain locus is retained on a chromosome fragment derived from a human. 
     
     
         7 . The human antibody-producing mouse of  claim 1 , wherein the human antibody κ light chain locus is inserted into a mouse chromosome. 
     
     
         8 . The human antibody-producing mouse of  claim 1 , which is not a chimeric mouse. 
     
     
         9 . A human antibody producing mouse, which carries (a) an unrearranged human antibody heavy chain locus, (b) an unrearranged human antibody κ light chain gene locus and (c) and unrearranged human antibody λ light chain gene locus, wherein at least one of (a), (b) and (c) is retained on a human derived chromosome fragment(s) and at least one of (a), (b) and (c) is inserted into a mouse chromosome, and further wherein at least both alleles of endogenous heavy chains and both alleles of endogenous k light chains are inactivated, and the mouse expresses human antibody heavy chain, human antibody κ light chain and human antibody λ light chain in the serum of the mouse. 
     
     
         10 . The human antibody producing mouse of  claim 9 , wherein the mouse carries an unrearranged human antibody heavy chain gene locus retained on a human derived chromosome fragment(s), an unrearranged human antibody κ light chain gene locus inserted into a mouse chromosome, and a human antibody λ light chain gene locus on a human derived chromosome fragment(s). 
     
     
         11 . The human antibody-producing mouse of  claim 9 , wherein the human antibody heavy chain gene locus is retained on a human derived chromosome fragment(s). 
     
     
         12 . The human antibody producing mouse of  claim 11 , wherein the human antibody heavy chain gene locus is retained on ΔHAC or ΔΔHAC. 
     
     
         13 . The human antibody producing mouse of  claim 9 , wherein the human antibody λ light chain gene locus is retained on a human derived chromosome fragment(s). 
     
     
         14 . The human antibody producing mouse of  claim 13 , wherein the human antibody λ light chain gene locus is retained on ΔHAC or ΔΔHAC. 
     
     
         15 . The human antibody producing mouse of  claim 9 , wherein the human antibody W light chain gene locus is inserted into the mouse chromosome. 
     
     
         16 . The human antibody producing mouse of  claim 15 , wherein the human antibody is transgene KCo5 is inserted into the mouse chromosome. 
     
     
         17 . The human antibody producing mouse of  claim 9 , wherein the human antibody heavy chain gene locus and λ light chain gene locus are retained on ΔHAC or ΔΔHAC, and human antibody κ transgene KCo5 is inserted into the mouse chromosome. 
     
     
         18 . The human antibody-producing mouse of  claim 9 , wherein the mouse is not a chimera mouse.