Ectopic expression of gamma interferon in the eyes of transgenic mice induces ocular pathology and MHC class II gene expression.
OBJECTIVE
To direct the expression of gamma IFN to the eyes of transgenic mice as a means of investigating the possible role of this lymphokine in ocular pathogenesis.


METHODS
Transgenic mouse strains were generated by injection of a DNA fragment containing the murine alpha A-crystallin promoter fused to the coding sequence of murine gamma IFN gene. PCR and RT-PCR were used to screen for the presence of the transgene and mRNA analyses, respectively. Methacrylate-embedded eye sections were analyzed for morphology and cryosections for immunoperoxidase antibody staining.


RESULTS
The most notable effects of gamma IFN in these transgenic mice include cataract, microphthalmia, blepharophimosis, microphakia, impairment of lens fiber formation, arrest of retinal differentiation, serous retinal detachment with presence of macrophages in the subretinal space, persistent hyperplastic primary vitreous, and corneal vascularization. MHC class II mRNA levels were significantly increased in the transgenic eyes and MHC class II proteins were expressed in their cornea, iris, ciliary body, choroid, lens and RPE.


CONCLUSIONS
Ectopic expression of gamma IFN in the lens affected the growth of the whole eye, resulting in microphthalmia and microphakia. The author's data suggest that alpha ACry-gamma IFN transgenic mouse ocular cells express functional gamma IFN receptors and that interaction of gamma IFN with its receptor induced biochemical and morphologic changes in the transgenic eyes. These mice provide an animal model for the study of the linkage between aberrant MHC expression and predisposition to autoimmune diseases.
Egwuagu
C E
CE
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
Sztein
J
J
Chan
C C
CC
Reid
W
W
Mahdi
R
R
Nussenblatt
R B
RB
Chepelinsky
A B
AB
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D003459:Crystallins / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics; D005128:Eye Diseases / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007908:Lens, Crystalline / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization
D003459:Crystallins; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D004247:DNA