RAG-2-deficient Mice Lack Mature Lymphocytes Owing to Inability to Initiate V(D)J Rearrangement

Cell. 1992 Mar 6;68(5):855-67. doi: 10.1016/0092-8674(92)90029-c.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • B-Lymphocytes / chemistry*
  • Base Sequence
  • DNA Nucleotidyltransferases / analysis*
  • DNA-Binding Proteins*
  • Gene Rearrangement, T-Lymphocyte / genetics*
  • Integrases*
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Phenotype
  • Proteins / analysis
  • Proteins / genetics*
  • Recombinases
  • T-Lymphocytes / chemistry*

Substances

  • Antibodies, Monoclonal
  • DNA-Binding Proteins
  • Proteins
  • Rag2 protein, mouse
  • Recombinases
  • V(D)J recombination activating protein 2
  • DNA Nucleotidyltransferases
  • Integrases
  • integron integrase IntI1