Characterization of immunoglobulin heavy chain knockout rats.
Eur J Immunol
; 40(10): 2932-41, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-21038471
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Região de Junção de Imunoglobulinas
/
Linfócitos B
/
Regiões Constantes de Imunoglobulina
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Transplante de Coração
/
Cadeias Pesadas de Imunoglobulinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França