Beyond Mice:Genetically Modifying Larger Animals to Model Human Diseases

Genetically modified animal models have been used widely to model human diseases for the purposes of investigating pathogenesis and developing therapeutic strategies.The genetic modification technology consists mainly of gene targeting and transgenic approaches,and genetic engineering to target genes in animals has now advanced to new technologies, such as zinc-finger nuclease(ZFN) and transcription activatorlike effector nuclease(TALEN).However,most animals used for creating disease models are still mice or other small animals. Despite the great advantages of genetically manipulating the genes of small animals,the disease models that result often do not accurately replicate the important pathological changes seen in human patients.For example,most transgenic mouse models of age-dependent neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,fail to show the overt neuronal loss seen in the brains of corresponding patients.This failure is believed to be due to