How to model aneuploidies?
Transgenesis and chromosome engineering At the DNA level, there is a problem of both scale and expression. The simplest approach to model segmental trisomy might be to generate mice bearing individual transgenes, in which a candidate gene of choice is expressed from an exogenous promoter; however, this is unlikely to re-create the correct overexpression dosage or the correct spatial and temporal patterns of expression. A further complication is that most transgene constructs use cDNAs and thus do not recapitulate the full set of splice isoforms expressed by many genes. A better approach is to use BAC or YAC transgenics, as here the gene(s) will be expressed from an endogenous promoter and are thus more likely to faithfully mirror expression (and splice variants) of the endogenous genes. However, even the largest YAC can only carry up to 1 2 Mb of DNA, and many well described partial trisomies are an order of magnitude larger than this. The solution to these problems of scale and expres
