US 11,891,618 B2
Mouse comprising a humanized TTR locus with a beta-slip mutation and methods of use
Jeffery Haines, New York, NY (US); Keith Crosby, Pleasantville, NY (US); Meghan Drummond Samuelson, Katonah, NY (US); David Frendewey, New York, NY (US); Brian Zambrowicz, Sleepy Hollow, NY (US); and Andrew J. Murphy, Croton-on-Hudson, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Jun. 3, 2020, as Appl. No. 16/891,571.
Claims priority of provisional application 62/856,999, filed on Jun. 4, 2019.
Prior Publication US 2020/0385760 A1, Dec. 10, 2020
Int. Cl. C12N 15/87 (2006.01); A01K 67/027 (2006.01)
CPC C12N 15/87 (2013.01) [A01K 67/0275 (2013.01); A01K 2227/105 (2013.01)] 28 Claims
 
1. A non human animal mouse comprising in its genome a genetically modified endogenous Ttr locus, wherein a region of the endogenous Ttr locus comprising both Ttr coding sequence and non-coding sequence has been deleted and replaced with a corresponding human TTR sequence comprising both TTR coding sequence and non-coding sequence, and wherein the genetically modified endogenous Ttr locus comprises a mutation that causes a shift in beta-strand D of the encoded transthyretin protein,
wherein the mutation is a triple mutation corresponding to G53S/E54D/L55S in the human transthyretin protein when the encoded transthyretin protein is optimally aligned with the human transthyretin protein.