Transgenic mouse model of retinal vascular disease, method of making, and method of using

A method for producing a transgenic mouse model of a retinal vascular disease, the method comprising:

• a) introducing DNA into a fertilized mouse egg, wherein the DNA encodes:
• (i) a constitutively active Akt mutant protein comprising an E40K or E17K substitution mutation;
• or (ii) a constitutively active Akt mutant protein in which a Plekstrin homology (PH) domain at the N-terminus has been replaced with a myristoylation signal sequence;
• and
• b) implanting the fertilized mouse egg obtained in step a) into a recipient embryo such that a transgenic mouse model of a retinal vascular disease is obtained,
• wherein the mouse model has a genome comprising a nucleic acid sequence encoding:
• (i) a constitutively active Akt mutant protein comprising an E40K or E17K substitution mutation;
• or (ii) a constitutively active Akt mutant protein in which a PH domain at the N-terminus has been replaced with a myristoylation signal sequence, wherein the mouse model shows at least one symptom selected from the group consisting of retinal edema, retinal hemorrhage, a retinal microaneurysm, and retinal vascular expansion.

A transgenic mouse whose genome comprises a nucleic acid sequence encoding a constitutively active Akt mutant protein:

• (i) comprising an E40K or E17K substitution mutation;
• or
• (ii) in which a Plekstrin homology (PH) domain at the N-terminus has been replaced with a myristoylation signal sequence,
• wherein the mouse is capable of developing at least one symptom selected from the group consisting of retinal edema, retinal hemorrhage, a retinal microaneurysm, and retinal vascular expansion after inducing expression of the constitutively active Akt mutant protein.