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Related Concept Videos

In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...

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Related Experiment Video

Updated: Jul 17, 2026

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
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Published on: July 14, 2016

VH replacement in mice and humans.

Zhixin Zhang1

  • 1Division of Developmental and Clinical Immunology, Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. zhixin.zhang@ccc.uab.edu

Trends in Immunology
|January 30, 2007
PubMed
Summary

Heavy chain variable segment (V(H)) replacement is a RAG-mediated process that can alter immunoglobulin genes. Evidence suggests this mechanism contributes to the antibody repertoire in mice and humans.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Heavy chain variable segment (V(H)) replacement involves secondary recombination between rearranged and unrearranged V(H) genes, mediated by recombination activating gene (RAG) products.
  • This process was initially observed in mouse pre-B cell lines and subsequently in knock-in mouse models with specific IgH gene configurations.

Purpose of the Study:

  • To review the evidence for V(H) replacement as an in vivo RAG-mediated mechanism for altering preformed IgH genes in both mice and humans.
  • To assess the contribution of V(H) replacement to the antibody repertoire.

Main Methods:

  • Review of existing literature and experimental findings on V(H) replacement in mice and humans.
  • Analysis of data from pre-B cell lines, knock-in mouse models, and human B cell samples.

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Main Results:

  • V(H) replacement has been observed in mouse models, but intermediates are difficult to detect during normal B cell development.
  • Ongoing V(H) replacement has been identified in human B cell lines and immature B cells, with potential products suggesting a role in antibody repertoire generation.

Conclusions:

  • V(H) replacement represents a potential in vivo RAG-mediated recombinatorial mechanism to modify IgH genes.
  • Further investigation is needed to fully elucidate the in vivo significance and extent of V(H) replacement in shaping the antibody repertoire in both species.