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US 2025/0113809 A1Published application
Genetically modified mouse models and methods of use thereof
AssigneeUniversity of South Florida
InventorLianchun Wang
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Abstract
The present disclosure relates to heparan sulfate transgenic models and methods of use thereof.
Claims20
A transgenic mouse comprising a nucleic acid sequence comprising a heterologous heparan sulfate-glucosamine 3-sulfotransferase (HS3ST) gene and at least two loxP nucleic acid sequences, and wherein a native HS3ST gene is deleted in the transgenic mouse.
A method of generating a transgenic HS3ST mouse, the method comprising:
- a. targeting a native HS3ST gene within a mouse with one or more single guide ribonucleic acid (sgRNA) sequences and a CRISPR-Cas9 system, wherein the CRISPR-Cas9 system excises the native HS3ST gene, and
- b. inserting a nucleic acid sequence to replace the native HS3ST gene, wherein the nucleic acid sequence comprises a heterologous HS3ST gene and at least two loxP nucleic acid sequences.
A method of screening for a therapeutic agent for treating or preventing a heparan sulfate-related disease, the method comprising:
- a. breeding a heparan sulfate-glucosamine 3-sulfotransferase (HS3ST) transgenic mouse with a Cre recombinase transgenic mouse to generate an HS3ST x Cre transgenic mouse, wherein the HS3ST transgenic mouse and the HS3ST x Cre transgenic mouse comprise a nucleic acid sequence comprising a heterologous HS3ST gene and at least two loxP nucleic acid sequences;
- b. activating expression of a Cre recombinase within the HS3ST x Cre transgenic mouse, wherein the Cre recombinase excises the heterologous HS3ST gene;
- c. inducing one or more phenotypes in the HS3ST x Cre transgenic mouse;
- d. administering the therapeutic agent to the HS3ST x Cre transgenic mouse;
- and
- e. detecting an improvement of the one or more phenotypes in the HS3ST x Cre transgenic mouse relative to an untreated transgenic mouse.
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Dependencies are inferred from the claim text.