**2.2 ESCs in genetic engineering and animal disease modeling**

Modern reproduction techniques make it possible for a single ESC to give rise to a whole animal, greatly simplifying the process of genetically engineering animals. Previously, animals were bred extensively to isolate beneficial random mutations fertilized eggs were microinjected with DNA for random genomic integration (Gordon et al., 1980), or engineered animals were derived from nuclear-cloned somatic cells that had been engineered to the desired genotype; such a technique was used to generate cattle that lacked the prion protein and were thus made completely immune to bovine spongiform encephalopathy (BSE; mad cow disease, which transmits to humans as the variant Creutzfeldt-Jakob)(Richt et al., 2006). ESCs are easier to genetically engineer due to their infinite self-renewability, allowing a very small number of drug- or marker-selected cells to regenerate a whole culture or stable cell line. This technique has been used to generate a variety of mouse genetic models including sickle cell disease (Wu et al., 2006), thalassemia (Ciavatta et al., 1995), microcephaly (Pulvers et al., 2010), and T-cell lymphoma (Pechloff et al., 2010), as well as a p53-knockout rat for cancer research (Tong et al., 2010).
