Figure 1.

Illustration of transgene construct and copy number. A: The target gene, usually its ORF, is linked to a promoter sequence that helps in targeting the transgene to the tissue or organ of interest. A promoter contains different transcription factor (TF) binding sites (TFB) and is activated upon binding by these TFs that usually act as homo- or hetero-dimers (indicated by the same or different shapes). Often a promoter is not very specific because the TFs bind to and regulate other genes as well. The TFs may also be expressed at different time points of the development, thus regulating the transgene at different ages of the life. B: In traditional technique, the transgene (dot) is randomly inserted into the genome, thus often being in different sites of a chromosome and in multiple chromosomes. If the mouse used as a breeder has two copies of the transgene on chromosome 2, one copy on chromosome 4 and another on chromosome 6 of either the paternal (dark bar) or the maternal (light grey bar) origin, during meiosis one of the two sister chromosomes of each chromosomal pair is randomly assigned to a sperm or egg, making different sperms or eggs having different copy numbers of the transgene (seven different genotypes are illustrated as examples). In reality the number of transgene-carrying pups may not meet the Mendelian inheritance because of natural selection for the healthier genotype.