Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain
Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.
대표청구항▼
1. A mouse whose germline genome comprises a modified endogenous mouse immunoglobulin heavy chain locus comprising a replacement of all functional endogenous mouse immunoglobulin heavy chain variable (VH) gene segments, all functional endogenous mouse immunoglobulin heavy chain diversity (DH) gene s
1. A mouse whose germline genome comprises a modified endogenous mouse immunoglobulin heavy chain locus comprising a replacement of all functional endogenous mouse immunoglobulin heavy chain variable (VH) gene segments, all functional endogenous mouse immunoglobulin heavy chain diversity (DH) gene segments and all functional endogenous mouse immunoglobulin heavy chain joining (JH) gene segments at the endogenous mouse immunoglobulin heavy chain locus with a nucleotide sequence that comprises a plurality of contiguous unrearranged functional human immunoglobulin light chain variable Vκ (hVκ) gene segments and all five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5), wherein the plurality of unrearranged functional hVκ gene segments and the five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5) are operably linked to an intact endogenous mouse immunoglobulin heavy chain constant region at the endogenous mouse immunoglobulin heavy chain locus,wherein the plurality of unrearranged functional hVκ gene segments and the five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5) rearrange in a B cell during B cell development to form a rearranged human immunoglobulin light chain variable region Vκ/Jκ nucleotide sequence operably linked to the endogenous mouse immunoglobulin heavy chain constant region at the endogenous mouse immunoglobulin heavy chain locus, andwherein the mouse comprises a CD19+ B cell comprising the rearranged human immunoglobulin light chain variable region Vκ/Jκ nucleotide sequence operably linked to the endogenous mouse immunoglobulin heavy chain constant region at the endogenous mouse immunoglobulin heavy chain locus. 2. The mouse of claim 1, wherein all the functional endogenous mouse VH, DH, and JH gene segments are replaced with at least 6 human Vκ gene segments and the five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5). 3. The mouse of claim 1, wherein all the functional endogenous mouse VH, DH, and JH gene segments are replaced with at least 16 human Vκ gene segments and the five contiguous unrearranged human immunoglobulin light chain joining gene segments (hJκ1-hJκ5). 4. The mouse of claim 1, wherein all the functional endogenous mouse VH, DH, and JH gene segments are replaced with at least 30 human Vκ gene segments and the five contiguous unrearranged human immunoglobulin light chain joining gene segments (hJκ1-hJκ5). 5. The mouse of claim 1, wherein all the functional endogenous mouse VH, DH, and JH gene segments are replaced with at least 40 human Vκ gene segments and the five contiguous unrearranged human immunoglobulin light chain joining gene segments (hJκ1-hJκ5). 6. An isolated cell from the mouse of claim 1, wherein the cell comprises a modified endogenous mouse immunoglobulin heavy chain locus comprising a replacement of all functional endogenous mouse immunoglobulin heavy chain variable (VH) gene segments, all functional endogenous mouse immunoglobulin heavy chain diversity (DH) gene segments and all functional endogenous mouse immunoglobulin heavy chain joining (JH) gene segments at the endogenous mouse immunoglobulin heavy chain locus with a nucleotide sequence that comprises a plurality of unrearranged functional human immunoglobulin light chain variable Vκ (hVκ) gene segments and all five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5), wherein the plurality of unrearranged functional hVκ gene segments and all five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5) are operably linked to an intact endogenous mouse immunoglobulin heavy chain constant region at the endogenous mouse immunoglobulin heavy chain locus,wherein the plurality of unrearranged functional hVκ gene segments and the five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5) are capable of rearranging in a B cell during B cell development to form a rearranged human immunoglobulin light chain variable region Vκ/Jκ nucleotide sequence operably linked to the endogenous mouse immunoglobulin heavy chain constant region at the endogenous mouse immunoglobulin heavy chain locus. 7. The isolated cell of claim 6, wherein the cell is an embryonic stem cell. 8. A cell isolated from the mouse of claim 1, wherein the cell is the CD19+ B cell. 9. A hybridoma comprising a myeloma cell line fused with the CD19+ B cell of claim 8, wherein the hybridoma produces a polypeptide encoded by the rearranged human immunoglobulin light chain variable region Vκ/Jκ nucleotide sequence operably linked to the endogenous mouse immunoglobulin heavy chain constant region. 10. The mouse of claim 1, wherein the rearranged human immunoglobulin light chain variable region Vκ/Jκ gene sequence comprises at least one N addition. 11. The mouse of claim 1, wherein the mouse is homozygous or heterozygous for the modified endogenous immunoglobulin heavy chain locus.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (23)
MacDonald, Lynn; Stevens, Sean; Murphy, Andrew J., ADAM6 mice.
Tomizuka, Kazuma; Yoshida, Hitoshi; Hanaoka, Kazunori; Oshimura, Mitsuo; Ishida, Isao, Chimeric mice that are produced by microcell mediated chromosome transfer and that retain a human antibody gene.
Allan Bradley ; Ramiro Ramirez-Solis ; Pentao Liu ; Hong Su ; Binhai Zheng, Method for chromosomal rearrangement by consecutive gene targeting of two recombination substrates to the deletion endpoints.
Hoogenboom, Hendricus Renerus Jacobus Mattheus; Logtenberg, Ton, Method for selecting a single cell expressing a heterogeneous combination of antibodies.
Surani Azim M. (Cambridge GB3) Neuberger Michael S. (Cambridge GB3) Bruggemann Marianne (Cambridge GB3), Production of antibodies from transgenic animals.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.