Genetically engineered non-human mammal, construction method therefor and use thereof
AssigneeMiao Wang
InventorsMiao Wang, Hong Chen
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Abstract
The present invention relates to genetically engineered non-human mammal and cells, organs and tissues; to use thereof in medicinal and disease research; to a method for producing non-human animals and cells, organs and tissues; and to a method for researching in medicine and disease by virtue of the non-human mammals or cells, organs or tissues.
Claims9
A genetically engineered non-human mammal, wherein the non-human mammal has a genome with the ApoE gene therein being disrupted so that ApoE is not expressed, and wherein the genome comprises (i) an exogenous nucleotide sequence encoding an siRNA against scavenger receptor class B type I (SR-BI), the exogenous nucleotide sequence being operably linked to an ApoE gene promoter, and (ii) one or more exogenous nucleotide sequences encoding a vasoconstrictor operably linked to an inducible promoter,
- wherein the exogenous nucleotide sequence encoding the siRNA and the one or more exogenous nucleotide sequences encoding the vasoconstrictor are inserted into the ApoE gene, and wherein the inserted exogeneous nucleotide sequence encoding the siRNA and the inserted one or more exogenous nucleotide sequences encoding the vasoconstrictor disrupt the ApoE gene so that ApoE is not expressed,
- wherein expression of the siRNA knocks down SR-BI expression in the liver of the non-human mammal,
- wherein the coding sequence of the siRNA has a homology of 100% to the sequence as shown in SEQ ID NO. 4,
- wherein the vasoconstrictor is angiotensin II,
- wherein the inducible promoter is a chemical-inducible promoter, and the chemical inducible promoter is a tetracycline-inducible promoter, and
- wherein the homozygous form of the genetically engineered non-human mammal displays hypercholesterolemia, hyperlipidemia, increase arteriosclerotic lesion formation, and hypertension as compared to the genetically engineered non-human mammal comprising a disruption of the ApoE gene so that ApoE is not expressed.
Cell, organ or tissue of a genetically engineered non-human mammal, wherein the non-human mammal has a genome with the ApoE gene therein being disrupted so that ApoE is not expressed, and wherein the genome comprises (i) an exogenous nucleotide sequence encoding an siRNA against scavenger receptor class B type I (SR-BI), the exogenous nucleotide sequence being operably linked to an ApoE gene promoter, and (ii) one or more exogenous nucleotide sequences encoding a vasoconstrictor operably linked to an inducible promoter,
- wherein the exogenous nucleotide sequence encoding the siRNA and the one or more exogenous nucleotide sequences encoding the vasoconstrictor are inserted into the ApoE gene, and wherein the inserted exogeneous nucleotide sequence encoding the siRNA and the inserted one or more exogenous nucleotide sequences encoding the vasoconstrictor disrupt the ApoE gene so that ApoE is not expressed,
- wherein expression of the siRNA knocks down SR-BI expression in the liver of the non-human mammal,
- wherein the coding sequence of the siRNA has a homology of 100% to the sequence as shown in SEQ ID NO. 4,
- wherein the vasoconstrictor is angiotensin II,
- wherein the inducible promoter is a chemical-inducible promoter, and the chemical inducible promoter is a tetracycline-inducible promoter, and
- wherein the homozygous form of the genetically engineered non-human mammal displays hypercholesterolemia, hyperlipidemia, increase arteriosclerotic lesion formation, and hypertension as compared to the genetically engineered non-human animal comprising a disruption of the ApoE gene so that ApoE is not expressed.
Dependencies are inferred from the claim text.