Biomaterial Database

Generation of a mouse strain that produces immunoglobulin kappa chains with human constant regions. 1993

Y R Zou, and H Gu, and K Rajewsky

Institute for Genetics, University of Cologne, Germany.

Humanized antibodies are highly efficient as immunotherapeutic reagents and have many advantages over rodent antibodies. A mouse strain was generated by gene targeting to replace the mouse kappa light chain constant (C) region gene with the human C kappa gene. Mice homozygous for the replacement mutation (C kappa R) produced normal concentrations of serum antibodies, most of which carry chimeric kappa light chains, and mounted normal immune responses to hapten-protein conjugates. This technology provides a feasible option for the generation of high-affinity humanized antibodies by means of the powerful somatic hypermutation-selection mechanism.

UI	MeSH Term	Description	Entries
D007127	Immunoglobulin Constant Regions	The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the C-terminus half of the IMMUNOGLOBULIN FAB FRAGMENT and two or three of them make up the rest of the heavy chains (all of the IMMUNOGLOBULIN FC FRAGMENT)	Ig Constant Regions,Immunoglobulin Constant Region,Constant Region, Ig,Constant Region, Immunoglobulin,Constant Regions, Ig,Constant Regions, Immunoglobulin,Regions, Ig Constant
D007132	Immunoglobulin Isotypes	The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties.	Antibody Class,Ig Isotype,Ig Isotypes,Immunoglobulin Class,Immunoglobulin Isotype,Antibody Classes,Immunoglobulin Classes,Class, Antibody,Class, Immunoglobulin,Classes, Antibody,Classes, Immunoglobulin,Isotype, Ig,Isotype, Immunoglobulin,Isotypes, Ig,Isotypes, Immunoglobulin
D007145	Immunoglobulin kappa-Chains	One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.	Ig kappa Chains,Immunoglobulins, kappa-Chain,kappa-Immunoglobulin Light Chains,Immunoglobulin kappa-Chain,kappa-Chain Immunoglobulins,kappa-Immunoglobulin Light Chain,kappa-Immunoglobulin Subgroup VK-12,kappa-Immunoglobulin Subgroup VK-21,Chains, Ig kappa,Immunoglobulin kappa Chain,Immunoglobulin kappa Chains,Immunoglobulins, kappa Chain,Light Chain, kappa-Immunoglobulin,Light Chains, kappa-Immunoglobulin,kappa Chain Immunoglobulins,kappa Chains, Ig,kappa Immunoglobulin Light Chain,kappa Immunoglobulin Light Chains,kappa Immunoglobulin Subgroup VK 12,kappa Immunoglobulin Subgroup VK 21,kappa-Chain, Immunoglobulin,kappa-Chains, Immunoglobulin
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011993	Recombinant Fusion Proteins	Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.	Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D005803	Genes, Immunoglobulin	Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).	Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein