The Use of Targeted Mutations in ES Cells to Create Novel Immunodeficient Mouse Models
The generation of the immune system is the only known developmental process in mammals that utilizes site-specific genomic recombination mechanisms. B lymphocyte differentiation occurs in fetal liver and adult bone marrow through a well-characterized pathway which includes the ordered assembly of immunoglobulin (Ig) heavy and light chain variable region genes followed by the expression of the assembled Ig chains (Alt et al. 1987, 1992). Likewise, T lymphocyte differentiation follows a similarly ordered program in the thymus, in which developing T cells rearrange and express T cell receptor (TCR)-β and -α chain genes (Davis and Bjorkman 1988; Malissen et al. 1992). Both Ig and TCR variable region genes are assembled by a common enzymatic process referred to as VDJ recombination (Tonegawa 1983; Blackwell and Alt 1989); the VDJ recombinase appears to be expressed only in developing B and T lymphocytes (Alt et al. 1992). The terminal differentiation of mature B cells may involve a different type of site-specific recombinational event referred to as heavy chain class-switch recombination (Blackwell and Alt 1989); this process allows the initially expressed μ constant region gene to be replaced by a different downstream CH gene, while maintaining the same variable region specificity.
KeywordsScid Mouse Light Chain Gene Variable Region Gene Scid Mutation Blastocyst Complementation
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