Targeted disruption of the porcine immunoglobulin kappa light chain locus

Inactivation of the endogenous pig immunoglobulin (Ig) loci, and replacement with their human counterparts, would produce animals that could alleviate both the supply and specificity issues of therapeutic human polyclonal antibodies (PAbs). Platform genetics are being developed in pigs that have all...

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Bibliographic Details
Published in:Transgenic research 2011-06, Vol.20 (3), p.643-653
Main Authors: Ramsoondar, J, Mendicino, M, Phelps, C, Vaught, T, Ball, S, Monahan, J, Chen, S, Dandro, A, Boone, J, Jobst, P, Vance, A, Wertz, N, Polejaeva, I, Butler, J, Dai, Y, Ayares, D, Wells, K
Format: Article
Language:English
Subjects:
Animal Genetics and Genomics
Animals
Antibodies
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biotechnology
Cloning
Cloning, Organism
Female
Fetuses
Fibroblasts
Fundamental and applied biological sciences. Psychology
Gene deletion
Gene Targeting
Genes, Immunoglobulin - genetics
Genetic Engineering
Genetic technics
Humans
Immunoglobulin kappa-Chains - genetics
Immunoglobulin kappa-Chains - metabolism
Immunoglobulins
Life Sciences
Light chains
Livestock
loci
Lymph nodes
Male
Methods. Procedures. Technologies
Molecular Medicine
mononuclear leukocytes
Nuclear Transfer Techniques
Original Paper
Peripheral blood mononuclear cells
Plant Genetics and Genomics
polyclonal antibodies
Sequence Deletion
somatic cell nuclear transfer
somatic cells
Swine
Transgenic animals and transgenic plants
Transgenics
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Summary:Inactivation of the endogenous pig immunoglobulin (Ig) loci, and replacement with their human counterparts, would produce animals that could alleviate both the supply and specificity issues of therapeutic human polyclonal antibodies (PAbs). Platform genetics are being developed in pigs that have all endogenous Ig loci inactivated and replaced by human counterparts, in order to address this unmet clinical need. This report describes the deletion of the porcine kappa (κ) light chain constant (Cκ) region in pig primary fetal fibroblasts (PPFFs) using gene targeting technology, and the generation of live animals from these cells via somatic cell nuclear transfer (SCNT) cloning. There are only two other targeted loci previously published in swine, and this is the first report of a targeted disruption of an Ig light chain locus in a livestock species. Pigs with one targeted Cκ allele (heterozygous knockout or ±) were bred together to generate Cκ homozygous knockout (−/−) animals. Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph nodes (MLNs) from Cκ −/− pigs were devoid of κ-containing Igs. Furthermore, there was an increase in lambda (λ) light chain expression when compared to that of wild-type littermates (Cκ +/+). Targeted inactivation of the Ig heavy chain locus has also been achieved and work is underway to inactivate the pig lambda light chain locus.
ISSN:0962-8819
1573-9368
DOI:10.1007/s11248-010-9445-y