RGD Reference Report - Characterization of immunoglobulin heavy chain knockout rats. - Rat Genome Database

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Characterization of immunoglobulin heavy chain knockout rats.

Authors: Ménoret, Séverine  Iscache, Anne-L  Tesson, Laurent  Rémy, Séverine  Usal, Claire  Osborn, Michel J  Cost, Gregory J  Brüggemann, Marianne  Buelow, Roland  Anegon, Ignacio 
Citation: Ménoret S, etal., Eur J Immunol. 2010 Oct;40(10):2932-41. doi: 10.1002/eji.201040939.
RGD ID: 150523760
Pubmed: PMID:21038471   (View Abstract at PubMed)
DOI: DOI:10.1002/eji.201040939   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IghmRatB cell deficiency  IMP  RGD 
Ighmem1AngRatB cell deficiency  IMP  RGD 
Ighmem2AngRatB cell deficiency  IMP  RGD 
SD-Ighmem1AngRatB cell deficiency  IMP  RGD 
SD-Ighmem2AngRatB cell deficiency  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IghmRatallograft rejection pathway  IMP  RGD 
Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IghmRatdecreased B cell number  IMP  RGD 
Ighmem1AngRatdecreased B cell number  IMP  RGD 
Ighmem2AngRatdecreased B cell number  IMP  RGD 
SD-Ighmem1AngRatdecreased B cell number  IMP  RGD 
SD-Ighmem2AngRatdecreased B cell number  IMP  RGD 
IghmRatdecreased IgA level  IMP  RGD 
Ighmem1AngRatdecreased IgA level  IMP  RGD 
Ighmem2AngRatdecreased IgA level  IMP  RGD 
SD-Ighmem1AngRatdecreased IgA level  IMP  RGD 
SD-Ighmem2AngRatdecreased IgA level  IMP  RGD 
IghmRatdecreased IgE level  IMP  RGD 
Ighmem1AngRatdecreased IgE level  IMP  RGD 
Ighmem2AngRatdecreased IgE level  IMP  RGD 
SD-Ighmem1AngRatdecreased IgE level  IMP  RGD 
SD-Ighmem2AngRatdecreased IgE level  IMP  RGD 
IghmRatdecreased IgG level  IMP  RGD 
Ighmem1AngRatdecreased IgG level  IMP  RGD 
Ighmem2AngRatdecreased IgG level  IMP  RGD 
SD-Ighmem1AngRatdecreased IgG level  IMP  RGD 
SD-Ighmem2AngRatdecreased IgG level  IMP  RGD 
IghmRatdecreased IgM level  IMP  RGD 
Ighmem1AngRatdecreased IgM level  IMP  RGD 
Ighmem2AngRatdecreased IgM level  IMP  RGD 
SD-Ighmem1AngRatdecreased IgM level  IMP  RGD 
SD-Ighmem2AngRatdecreased IgM level  IMP  RGD 
IghmRatincreased length of allograft survival  IMP  RGD 
Ighmem1AngRatincreased length of allograft survival  IMP  RGD 
Ighmem2AngRatincreased length of allograft survival  IMP  RGD 
SD-Ighmem1AngRatincreased length of allograft survival  IMP  RGD 
SD-Ighmem2AngRatincreased length of allograft survival  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ighm  (immunoglobulin heavy constant epsilon)
Ighmem1Ang  (immunoglobulin heavy constant mu; ZFN induced mutant1, Ang)
Ighmem2Ang  (immunoglobulin heavy constant mu; ZFN induced mutant2, Ang)

SD-Ighmem1Ang  (NA)
SD-Ighmem2Ang  (NA)

Additional Information