Mouse model of ditra disease and uses thereof
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsAndrew J. Murphy, Alexander O. Mujica, Ka-Man Venus Lai, Sokol Haxhinasto
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Abstract
This disclosure relates to genetically modified rodent animals and rodent models of human diseases. More specifically, this disclosure relates to genetically modified rodents whose genome comprises a humanized Il1rl2 gene (coding for the IL1rl2 subunit of the IL-36R protein) and human IL-36α, β and γ ligand genes. The genetically modified rodents disclosed herein display enhanced skin and intestinal inflammation as a preclinical model of psoriasis and IBD, respectively, and serve as a rodent model of human DITRA disease.
Claims10
-45. (canceled)
A combination of a first targeting nucleic acid construct and a second targeting nucleic acid construct,
- wherein the first targeting nucleic acid construct comprises a nucleotide sequence of a human IL1RL2 gene, flanked by 5′ and 3′ mouse nucleotide sequences capable of mediating homologous recombination and integration of the nucleotide sequence of a human IL1RL2 gene into a mouse Il1rl2 gene to form a humanized Il1rl2 gene, wherein the humanized Il1rl2 gene encodes a humanized Il1rl2 protein that comprises the ectodomain of a human IL1RL2 protein and the transmembrane-cytoplasmic domains of a mouse Il1rl2 protein;
- and
- wherein the second targeting nucleic acid construct comprises a contiguous nucleic acid sequence comprising a human IL1F6 gene, a human IL1F8 gene, and a human IL1F9 gene, wherein the contiguous nucleic acid sequence is flanked by 5′ and 3′ mouse nucleotide sequences capable of mediating homologous recombination and integration of the contiguous nucleic acid sequence into the mouse genomic DNA encompassing the mouse Il1f6 gene, the mouse Il1f8 gene, and the mouse Il1f9 gene.
Dependencies are inferred from the claim text.