Transgenic ungulates having reduced prion protein activity and uses thereof

A bovine cell comprising a non-naturally occurring mutation in one or both alleles of an endogenous prion nucleic acid.

A method for producing a transgenic bovine cell having reduced expression of functional prion protein, comprising introducing a first prion gene targeting vector into a bovine cell under conditions that allow homologous recombination between said first vector and a first allele of an endogenous prion nucleic acid in said cell, thereby introducing a hemizygous mutation in said cell.

A method for producing a transgenic bovine having reduced expression of functional prion protein, said method comprising the steps of:

• (a) inserting a cell, a chromatin mass from a cell, or a nucleus from a cell into an oocyte, wherein said cell comprises a first mutation in an endogenous prion nucleic acid;
• and
• (b) transferring said oocyte or an embryo formed from said oocyte into the uterus of a host bovine under conditions that allow said oocyte or said embryo to develop into a fetus.