| 摘要 |
Disclosed is the use of a mouse for producing immunoglobulin (Ig) light chains in B cells having a normal proportion of mature splenic B cells, wherein the mouse expresses Ig light chains bearing human lambda variable regions and immunoglobulin light chains bearing human kappa variable regions, wherein more than 30 % of the light chains expressed by the mouse comprise lambda variable regions, wherein the mouse genome comprises an Ig gene segment repertoire produced by targeted insertion of human Ig gene segments into one or more endogenous Ig loci, the genome comprising human Vλ and Jλ gene segments provided by insertion into an endogenous light chain locus of the vertebrate upstream of a constant region, wherein the human Vλ and Jλ insertion comprises at least human V gene segments Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3 and Vλ3-1 and one, more or all of human J gene segments Jλ1, Jλ2, Jλ3, Jλ6 and Jλ7, the genome comprising human V&kgr; and J&kgr; gene segments provided by insertion into an endogenous kappa light chain locus of the mouse upstream of a kappa constant region, wherein the human V&kgr; and J&kgr; insertion comprises at least human V gene segments V&kgr;1-33, V&kgr;2-30, V&kgr;2-29, V&kgr;2-28, V&kgr;1-27, V&kgr;2-24, V&kgr;3-20, V&kgr;1-17, V&kgr;1-16, V&kgr;3-15, V&kgr;1-13, V&kgr;1-12, V&kgr;3-11, V&kgr;1-9, V&kgr;1-8, V&kgr;1-6, V&kgr;1-5, V&kgr;5-2 and V&kgr;4-1 and one, more or all of human J gene segments J&kgr;1, J&kgr;2, J&kgr;3, J&kgr;4 and J&kgr;5, wherein endogenous kappa chain expression is inactive, and wherein at least 50 % of total splenic B cells produced by the mouse are mature B cells. |
