Methods for Modifying Eukaryotic Cells
A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
1 . A cell comprising a light chain immunoglobulin locus comprising a human light chain variable region and a non-human light chain constant region.
2 . The cell of claim 1 , wherein light chain constant region is a mouse light chain constant region.
3 . The cell of claim 1 , wherein the light chain immunoglobulin locus is a kappa light chain locus.
4 . The cell of claim 1 , wherein the light chain immunoglobulin locus is a lambda light chain locus.
5 . The cell of claim 1 , wherein the human light chain variable region is unrearranged.
6 . The cell of claim 1 , wherein the light chain immunoglobulin locus is an endogenous light chain immunoglobulin locus.
7 . The cell of claim 1 , wherein the mouse expresses an antibody having a light chain encoded by the light chain immunoglobulin locus.
8 . The cell of claim 2 , wherein the cell produces an antibody that comprises a human light chain variable region and a mouse light chain constant region.
9 . The cell of claim 1 , wherein the cell does not comprise a human immunoglobulin light chain constant region.
10 . The cell of claim 1 , wherein the cell is an ES cell, a hybridoma or a CHO cell.
11 . A cell comprising:
a light chain immunoglobulin locus comprising a human light chain variable region and a non-human light chain constant region; and
a heavy chain immunoglobulin locus comprising a human heavy chain variable region.
12 . The cell of claim 11 , wherein the light chain immunoglobulin locus is a kappa light chain locus.
13 . The cell of claim 11 , wherein the light chain immunoglobulin locus is a lambda light chain locus.
14 . The cell of claim 11 , wherein the non-human light chain constant region is a mouse light chain constant region.
15 . The cell of claim 11 , wherein the heavy chain immunoglobulin locus further comprises a non-human heavy chain constant region.
16 . The cell of claim 11 , wherein the human heavy chain variable region is unrearranged.
17 . The cell of claim 16 , wherein the human light chain variable region is unrearranged.
18 . The cell of claim 11 , wherein the mouse expresses an antibody having a light chain encoded by the light chain immunoglobulin locus and a heavy chain encoded by the heavy chain immunoglobulin locus.
19 . The cell of claim 14 , wherein the mouse produces an antibody that comprises a human light chain variable region and a mouse light chain constant region.
20 . The cell of claim 1 , wherein the cell is an ES cell, a hybridoma or a CHO cell.