Tg mice expressing either a chimeric elk/mouse PrP, a chimeric horse/mouse PrP, or the I109 variant of BVPrP, all of which contain a rigid loop, develop a spontaneous neurologic illness reminiscent of prion disease [33], [62], [63], suggesting that the presence of a rigid loop may render PrP more prone to misfolding. This evidence concerns the gene PRNP and prion disease.