Rodents having a humanized tmprss gene
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsLisa Purcell, Alexander O. Mujica, Yajun Tang
Life of this patent
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Abstract
Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.
Claims22
A rodent comprising a humanized Tmprss gene that comprises a nucleotide sequence of an endogenous rodent Tmprss gene and a nucleotide sequence of a cognate human TMPRSS gene, wherein the humanized Tmprss gene is under control of the promoter of the endogenous rodent Tmprss gene.
-37. (canceled)
An isolated rodent cell or tissue whose genome comprises a humanized Tmprss gene that comprises a nucleotide sequence of an endogenous rodent Tmprss gene and a nucleotide sequence of a cognate human TMPRSS gene, wherein the humanized Tmprss gene is under control of the promoter of the endogenous rodent Tmprss gene.
(canceled)
(canceled)
A vector comprising a human genomic DNA encoding the ectodomain of a human TMPRSS protein, flanked by a 5′ nucleotide sequence and a 3′ nucleotide sequence that are homologous to genomic DNA sequences flanking a rodent genomic DNA at a rodent Tmprss locus encoding the ectodomain of a cognate rodent Tmprss protein.
A method of providing a rodent whose genome comprises a humanized Tmprss gene, the method comprising:
- modifying the genome of a rodent to replace a genomic sequence of an endogenous Tmprss gene with a genomic sequence of a cognate human TMPRSS gene to form a humanized Tmprss gene.
A method of making a rodent having a humanized Tmprss gene, comprising:
- (a) inserting a genomic fragment into an endogenous rodent Tmprss locus in a rodent embryonic stem cell, said genomic fragment comprising a nucleotide sequence of a cognate human TMPRSS gene, thereby forming a humanized Tmprss gene, wherein the humanized Tmprss gene is under control of the promoter of the rodent Tmprss gene at the endogenous rodent Tmprss locus;
- (b) obtaining a rodent embryonic stem cell comprising the humanized Tmprss gene of (a);
- and,
- (c) creating a rodent using the rodent embryonic stem cell of (b).
-61. (canceled)
A method of assessing the therapeutic efficacy of a compound in treating influenza virus infection, comprising:
- administering an influenza virus and a candidate compound to a rodent comprising a humanized Tmprss gene that comprises a nucleotide sequence of an endogenous rodent Tmprss gene and a nucleotide sequence of a cognate human TMPRSS gene, wherein the humanized Tmprss gene is under control of the promoter of the endogenous rodent Tmprss gene;
- and
- monitoring the presence and severity of influenza virus infection in the rodent to determine the therapeutic efficacy of the candidate compound.
-67. (canceled)
Dependencies are inferred from the claim text.