Characterization of immunoglobulin heavy chain knockout rats

The rat is a species frequently used in immunological studies but, until now, there were no models with introduced gene-specific mutations. In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we comp...

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Bibliographic Details
Published in:	European journal of immunology Vol. 40; no. 10; pp. 2932 - 2941
Main Authors:	Ménoret, Séverine, Iscache, Anne-L, Tesson, Laurent, Rémy, Séverine, Usal, Claire, Osborn, Michel J, Cost, Gregory J, Brüggemann, Marianne, Buelow, Roland, Anegon, Ignacio
Format:	Journal Article
Language:	English
Published:	Weinheim Wiley-VCH Verlag 01-10-2010 WILEY‐VCH Verlag Wiley Subscription Services, Inc
Subjects:	Amino Acid Sequence Animals Animals, Genetically Modified B-Lymphocytes - cytology B-Lymphocytes - immunology B‐cell deficient Cell Differentiation - immunology Embryonic Stem Cells - immunology Graft Survival - immunology Heart Transplantation - immunology Immunoglobulin Constant Regions - genetics Immunoglobulin Constant Regions - immunology Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Isotypes - blood Immunoglobulin Joining Region - genetics Immunoglobulin Joining Region - immunology Knockout rat Lymphoid Tissue - immunology Molecular Sequence Data Rats Rats, Inbred Lew Rats, Mutant Strains Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction RNA - chemistry RNA - genetics Specific Pathogen-Free Organisms Transgenic rat Zinc Fingers - genetics Zinc‐finger nucleases
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Summary:	The rat is a species frequently used in immunological studies but, until now, there were no models with introduced gene-specific mutations. In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we compare immune development in two Ig heavy-chain KO lines; one with truncated Cμ and a new line with removed JH segments. Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH-deletion rats showed undetectable mRNA for all H-chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B-cell numbers were reduced >95% versus WT animals. In rats homozygous for IgM mutation, no Ab-mediated hyperacute allograft rejection was encountered. Similarities in B-cell differentiation seen in Ig KO rats and ES cell-derived Ig KO mice are discussed. These Ig and B-cell-deficient rats obtained using zinc-finger nucleases-technology should be useful as biomedical research models and a powerful platform for transgenic animals expressing a human Ab repertoire.
Bibliography:	http://dx.doi.org/10.1002/eji.201040939 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2980 1521-4141
DOI:	10.1002/eji.201040939