Related Experiment Video
Updated: Feb 11, 2026
09:35
Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
Published on: April 20, 2021
7.3K
Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double-knockout mice
Hong Ming Shen1, Atsushi Tanaka, Grazyna Bozek
1Department of Molecular Genetic and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 4, 2006
Summary
Activation-induced deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR). In Ung(-/-)Msh6(-/-) mice, AID activity is restricted in vivo, with C,G transitions as key mutation footprints.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Somatic hypermutation (SHM) and class switch recombination (CSR) are crucial adaptive immune processes initiated by activation-induced cytosine deaminase (AID).
- Error-prone repair pathways, including base excision repair (BER) and mismatch repair (MMR), process AID-generated uracil lesions, influencing mutation outcomes.
- Previous studies indicated that deficiencies in Ung, Msh2, or Msh6 impact SHM and CSR.
Purpose of the Study:
- To investigate the role of Msh2/Msh6 complexes in SHM and CSR by analyzing these processes in Msh6(-/-)Ung(-/-) mice.
- To determine if Msh2/Msh6 complexes are the sole mismatch-recognition complexes required for SHM and CSR.
- To elucidate the in vivo activity and mutational footprints of AID.
Main Methods:
- Analysis of somatic hypermutation (SHM) and class switch recombination (CSR) in Msh6(-/-)Ung(-/-) mice.
- Comparison of mutation profiles and CSR efficiency with previously studied Msh2(-/-)Ung(-/-) mice.
- Assessment of AID activity based on mutation patterns, particularly C,G transitions.
Main Results:
- SHM and CSR were similarly affected in Msh6(-/-)Ung(-/-) mice as in Msh2(-/-)Ung(-/-) mice, with predominantly C,G transitions and significantly reduced CSR.
- Inactivation of Ung alone reduced A,T mutations, suggesting a role for error-prone long-patch BER in generating these mutations.
- The 5' and 3' regions of Ig genes remained mutation-free, consistent with wild-type mice, indicating AID's spatial restriction in vivo.
Conclusions:
- Msh2/Msh3 contributions to SHM and CSR appear unlikely, as Msh6(-/-)Ung(-/-) mice exhibit similar defects to Msh2(-/-)Ung(-/-) mice.
- The data suggest that transition mutations from C and G in Ung(-/-)Msh6(-/-) mice serve as reliable "footprints" of AID activity.
- In vivo, AID activity is significantly restricted compared to its activity in cell-free assays.
Related Concept Videos
02:04Fixing Double-strand Breaks
14.9K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
14.9K
01:22Switching of BJT
873
Switching behavior in Bipolar Junction Transistors (BJTs) is a fundamental aspect utilized in various electronic circuits, particularly for digital logic applications like switches and amplifiers. In a typical switching circuit, a BJT alternates between cut-off and saturation modes, corresponding to the "off" and "on" states, respectively, thus behaving like an ideal switch.
Cut-off Mode ("Off" State): In this state, both the emitter-base and collector-base junctions are...
Cut-off Mode ("Off" State): In this state, both the emitter-base and collector-base junctions are...
873
02:31Homologous Recombination
63.5K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
63.5K
01:09Recombinant DNA
103.5K
Overview
103.5K
00:57Viral Recombination
25.2K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
25.2K
02:53Conservative Site-specific Recombination and Phase Variation
6.9K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.9K