Production Of Prion Protein Gene (PRNP) Knockout Goats By Somatic Gene Targeting.

Prion diseases, also called transmissible spongiform encephalopathies (TSE), area group of lethal infectious neurodegenerative disorders of the central nervous system.The most notable examples of these diseases are scrapie in sheep and goats, bovinespongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD),Gerstmann-Straussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) inhuman beings.The cellular prion protein (PrPC), a membrane glycoprotein anchored to the outersurface of neurons, lymphocytes and other cells, is directly associated with thepathogenesis of the transmissible spongiform encephalopathies (TSE). Although micelacking PrPC develop and reproduce normally and are resistant to scrapie infection,large animals lacking PrPC, especially those species in which TSE naturally occurs,are currently not available.Here, we report, for the first time, five live PRNP+/-cloned goats. RNA andprotein analysis of one dead PRNP+/-goat showed that one allele of the caprine PRNPgene had been functionally disrupted on the RNA transcription level and the PrPCexpression level in its brain was apparently reduced. All the five PRNP+/-goats shownormal development and behavior up to at least six months of age. Theseheterozygous PRNP+/-goats are ready to be used in producing homozygous PRNP-/-goats in which no PrPC should be expressed.