History of Humanized Mice
“Historically, genetic humanization of model organisms was achieved through one of two methods: random insertion transgenic humanization and targeted genomic humanization. Random insertion transgenic humanization technology for the mouse was introduced in the 1980s and allowed researchers to randomly insert human genetic material, which could include an entire gene and its promoter, into the mouse genome. . . . In contrast, targeted genomic humanization removes much of the uncertainty associated with random insertion of human transgenes by inserting a single copy of a transgene at a desired location in the host. The process is more complex, expensive, and time consuming, but the transgene insertion is predictable and results in easier breeding. This strategy is typically used to replace the first exon of a mouse gene with the corresponding cDNA of a human gene, simultaneously inactivating the mouse gene and introducing the human gene for expression driven by the existing mouse promoter. The primary disadvantage of this method is its artificiality of regulation: any pre-mRNA splicing regulation that may have occurred in the human gene is lost and 3’ UTRs are typically not included in transgenes.” MORE
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