NR AVQD
AU Richt,J.A.; Kasinathan,P.; Hamir,A.N.; Castilla,J.; Sathiyaseelan,T.; Vargas,F.; Sathiyaseelan,J.; Wu,H.; Matsushita,H.; Koster,J.; Kato,S.; Ishida,I.; Soto,C.; Robl,J.M.; Kuroiwa,Y.
TI Production of cattle lacking prion protein
QU Nature Biotechnology 2006 Dec 31
PT journal article
AB Prion diseases are caused by propagation of misfolded forms of the normal cellular prion protein PrPc, such as PrP(BSE) in bovine spongiform encephalopathy (BSE) in cattle and PrP(CJD) in Creutzfeldt-Jakob disease (CJD) in humans. Disruption of PrPc expression in mice, a species that does not naturally contract prion diseases, results in no apparent developmental abnormalities. However, the impact of ablating PrPc function in natural host species of prion diseases is unknown. Here we report the generation and characterization of PrPc-deficient cattle produced by a sequential gene-targeting system. At over 20 months of age, the cattle are clinically, physiologically, histopathologically, immunologically and reproductively normal. Brain tissue homogenates are resistant to prion propagation in vitro as assessed by protein misfolding cyclic amplification. PrPc-deficient cattle may be a useful model for prion research and could provide industrial bovine products free of prion proteins.
AD Jürgen A. Richt (jricht@nadc.ars.usda.gov), Amir N. Hamir, Francisco Vargas, National Animal Disease Center, Agriculture Research Services, United States Department of Agriculture, 2300 Dayton Avenue, Ames, Iowa 50010, USA; Poothappillai Kasinathan, Thillai Sathiyaseelan, Janaki Sathiyaseelan, Hua Wu, Hiroaki Matsushita, Julie Koster, James M. Robl (jrobl@hematech.com), Hematech, Inc., 4401 S. Technology Drive, Sioux Falls, South Dakota 57106, USA; Joaquin Castilla, Claudio Soto, Department of Neurology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555-0646, USA; Shinichiro Kato, Isao Ishida, Yoshimi Kuroiwa (ykuroiwa@hematech.com), Pharmaceutical Division, Kirin Brewery Co., Ltd., 26-1, Jingumae 6-chome, Shibuya-ku, Tokyo, Japan; Shinichiro Kato, Yoshimi Kuroiwa, Gemini Science Inc., 9420 Athena Circle, La Jolla, California 92109, USA
SP englisch