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  • Title: Human immunoglobulin transgenes undergo rearrangement, somatic mutation and class switching in mice that lack endogenous IgM.
    Author: Taylor LD, Carmack CE, Huszar D, Higgins KM, Mashayekh R, Sequar G, Schramm SR, Kuo CC, O'Donnell SL, Kay RM.
    Journal: Int Immunol; 1994 Apr; 6(4):579-91. PubMed ID: 8018598.
    Abstract:
    We have generated transgenic mice that contain human-sequence Ig miniloci and, because they are also homozygous for a targeted disruption of their endogenous heavy chain genes, must rely on the transgene sequences for B cell receptor expression. Although the human transgenes contain only a fraction of the intact human heavy chain locus, these defined sequences are able to at least partially restore the humoral immune system in the mouse. B cells expressing human heavy chains develop in the bone marrow, populate peripheral lymphoid tissue and respond specifically to antigen. Furthermore, the heavy chain transgenes contain both human mu and gamma 1 coding exons as well as the respective mu and gamma 1 switch regions. The sequences included within the transgene are sufficient to direct class switch recombination. Transgene sequences are also sufficient to direct somatic mutation of the class-switched heavy chain genes. These observations define the upper limit of the cis-acting sequences necessary to direct heavy chain class switching and somatic mutation.
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