Genetically Engineered Mouse Models of Prostate Cancer Martijn C. Nawijn, Andreas M. Bergman, Henk G. van der Poel  European Urology Supplements  Volume 7, Issue 8, Pages 566-575 (August 2008) DOI: 10.1016/j.eursup.2008.01.019 Copyright © 2008 European Association of Urology and European Board of Urology Terms and Conditions

Fig. 1 Genetic engineering of the mouse germline. Most genes present in the mouse genome will contain several exons, indicated as open rectangles, spaced by the noncoding intervening sequences known as introns. Gene expression is controlled by regulatory sequences positioned upstream of the transcription initiation site (both enhancer and promoter sequences), in the intronic sequences or downstream of the last exon (depicted schematically as the black arrow). (B) Single gene knockouts are generated by replacing most of the coding sequences, or a critical part of the coding sequence, by unrelated sequences. Expression from the endogenous locus will result in a nonfunctional protein. The knockout allele is often referred to as a null allele. (C) Multicopy transgenics are generated by genomic insertion of multiple copies of a transgene, usually the cDNA sequence of the gene of interest (indicated as the fused open rectangles) placed under transcriptional regulation of a generic or cell-type specific promoter sequence (indicated by the grey arrow). Transgene integration occurs at a random position in the genome, and copy numbers vary between individual founder mice, allowing for the selection of high- and low-copy transgenic strains. (D) Conditional knockout strains are generated by the introduction of loxP sequences (indicated as solid triangles) at opposite ends of the gene of interests. Expression (usually transgenic) of the Cre recombinase will result in fusion of the two loxP sites, with excision of the intervening sequences, in this case most of the coding sequence of the gene. Hence, a conditional knockout allele allows the normal developmental expression pattern of the gene up to the moment when Cre recombinase is introduced into the (somatic) cells. Depending on the expression pattern of the Cre transgene, this approach allows the generation of tissue-specific knockouts. (E) Conditional transgenic strains are generated by the introduction of a conditional STOP cassette upstream of the coding sequences of the transgene of interest. The STOP cassette abrogates translation from the mRNA and precludes expression of the transgene. Introduction of Cre recombinase results in removal of the STOP cassette and thereby induces expression of the transgene. The expression pattern of the Cre recombinase determines the tissue-specific activation of the transgene. European Urology Supplements 2008 7, 566-575DOI: (10.1016/j.eursup.2008.01.019) Copyright © 2008 European Association of Urology and European Board of Urology Terms and Conditions