RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement

Shinkai, Y·1992·Cell

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Abstract

We have generated mice that carry a germline mutation in which a large portion of the RAG-2 coding region is deleted. Homozygous mutants are viable but fail to produce mature B or T lymphocytes. Very immature lymphoid cells were present in primary lymphoid organs of mutant animals as defined by surface marker analyses and Abelson murine leukemia virus (A-MuLV) transformation assays. However, these cells did not rearrange their immunoglobulin or T cell receptor loci. Lack of V(D)J recombination activity in mutant pre-B cell lines could be restored by introduction of a functional RAG-2 expression vector. Therefore, loss of RAG-2 function in vivo results in total inability to initiate V(D)J rearrangement, leading to a novel severe combined immune deficient (SCID) phenotype. Because the SCID phenotype was the only obvious abnormality detected in RAG-2 mutant mice, RAG-2 function and V(D)J recombinase activity, per se, are not required for development of cells other than lymphocytes.

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Authors: Shinkai, Y.
Venue: Cell
Publisher: Elsevier BV
Published: 1992-03-06
Volume: 68
Issue: 5
Pages: 855-867
ISSN: 0092-8674
DOI: 10.1016/0092-8674(92)90029-c
Cited by: 2,150
References: 0
Language: en
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement

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