US 12,250,931 B2
Genetically modified mouse with a humanized PNPLA3 gene and methods of use
Xiping Cheng, Northvale, NJ (US); Jose F. Rojas, Newburgh, NY (US); and Mark Sleeman, New York, NY (US)
Assigned to REGENERON PHARMACEUTICALS, INC., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Jan. 27, 2021, as Appl. No. 17/159,564.
Claims priority of provisional application 62/966,837, filed on Jan. 28, 2020.
Prior Publication US 2021/0227812 A1, Jul. 29, 2021
Int. Cl. A01K 67/027 (2024.01); A01K 67/0278 (2024.01); A61K 49/00 (2006.01); C12N 15/85 (2006.01)
CPC A01K 67/0278 (2013.01) [A61K 49/0008 (2013.01); C12N 15/8509 (2013.01); A01K 2207/15 (2013.01); A01K 2227/105 (2013.01)] 23 Claims
 
1. A genetically modified mouse whose genome comprises a humanized patatin-like phospholipase domain containing 3 (PNPLA3) gene comprising an endogenous PNPLA3 promoter, and a replacement of an endogenous nucleic acid sequence from the first exon through the penultimate exon including all intervening introns of a PNPLA3 gene with an exogenous nucleic acid sequence comprising the start codon through the stop codon of a human PNPLA3 gene,
wherein the mouse functionally expresses human PNPLA3 and exhibits increased expression of PNLPA3 in liver tissue when given standard chow as compared to a wild-type mouse given standard chow.