Humanized mouse models for study of covid-19
OwnerChenYen Lai, Oscar Alvarez +1inventors
InventorsChenYen Lai, Oscar Alvarez, Kurt Jarnagin
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Abstract
The present disclosure relates to genetically modified non-human animals (e.g., genetically-modified mice or rodents) that express a hACE2 and/or hTMPRRS2 under control of the mouse promoter and the genetically modified non-human animal does not express native ACE2 and/or hTMPRRS2. The present disclosure also relates to methods of generating the genetically-modified animals (e.g., genetically modified mice or rodents), and methods of using the genetically modified non-human animals (e.g., genetically modified mice or rodents) described herein.
Claims27
A construct comprising a human ACE2 cDNA minigene, the human ACE2 cDNA minigene comprising a start codon, and an SV40 mini-intron comprising a splice donor site and a splice acceptor site within the cDNA sequence of human ACE2.
A construct comprising a human TMPRSS2 cDNA minigene, the human TMPRSS2 cDNA minigene comprising a start codon, and an SV40 mini-intron comprising a splice donor site and a splice acceptor site within the cDNA sequence of human TMPRSS2.
A genetically-modified mouse comprising in its genome at least one chromosome comprising a nucleic acid sequence encoding a human cDNA ACE2 minigene, wherein the mouse does not express endogenous ACE2.
A genetically-modified mouse comprising it its genome at least one chromosome comprising a nucleic acid sequence encoding a human cDNA TMPRSS2 minigene, wherein the mouse does not express endogenous TMPRSS2.
A method of making a genetically-modified mouse, the method comprising replacing in at least one cell of the animal, at an endogenous ACE2 gene locus, a sequence encoding a region of an endogenous ACE2 with a sequence encoding a corresponding region of human cDNA ACE2 minigene.
Dependencies are inferred from the claim text.