Production of Transgenic Male Piglet as Research Model for Alzheimer's Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with memory loss and cognitive impairments. An AD transgenic (Tg) pig model would be useful for preclinical testing of therapeutic agents. In this study, we report the use of somatic cell nuclear transfer (SCNT) to produce transgenic pigs over-expressing the human AD related genes (APP, APPswedish, Presenilin 1, and Tau). Transgenic embryos were generated by SCNT of from ear fibroblasts expressing AD genes. A total of 1808 (average 258) SCNT embryos were transferred into 7 recipients. Pregnancy was successfully maintained in one recipient. We obtained 1 cloned male piglet from a surrogate gilts and the weight of piglet was 935 g. But, the male piglet died two days after birth. The piglet expressed AD related genes by PCR and western blot analysis. Transgenes were expressed in multiple tissues, and at especially high levels in brain. AD Tg pig might be very useful for studying the disease and for testing new therapeutics in preclinical studies of human AD.