Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2

UMMS Affiliation

Department of Molecular Genetics and Microbiology

Publication Date


Document Type



Animals; Antibody Diversity; DNA Primers; DNA-Binding Proteins; Immunoglobulin Class Switching; Immunoglobulin Switch Region; Mice; Mice, Knockout; *Models, Genetic; MutS Homolog 2 Protein; Polymerase Chain Reaction; Proto-Oncogene Proteins; Tandem Repeat Sequences


Life Sciences | Medicine and Health Sciences | Women's Studies


The mechanisms that target class switch recombination (CSR) to antibody gene switch (S) regions are unknown. Analyses of switch site locations in wild-type mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4-5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for switching independent of Smu sequences. This CSR-accessible domain is reminiscent of the promoter-defined domains that target somatic hypermutation. Within the 4-5-kb CSR domain, the targeting of S site locations also depends on the Msh2 mismatch repair protein because Msh2-deficient mice show an increased focus of sites to the Smu tandem repeat region. We propose that Msh2 affects S site location because sequences with few activation-induced cytidine deaminase targets generate mostly switch DNA cleavages that require Msh2-directed processing to allow CSR joining.

DOI of Published Version



J Exp Med. 2005 Jun 20;201(12):1885-90. Epub 2005 Jun 13. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of experimental medicine

Related Resources

Link to article in PubMed

PubMed ID