Microphthalmia and lack of vitreous body in transgenic mice expressing the first immunoglobulin-like domain of nectin-1.
BACKGROUND
Nectins are Ca2+-independent immunoglobulin (Ig)-like cell-cell-adhesion molecules. We have generated transgenic mice expressing a series of soluble forms of nectin-1, and investigated special effects of each soluble form of nectin-1 in vivo. In the course of generating transgenic mice expressing a soluble form of nectin-1 consisting of the first Ig-like domain of nectin-1 and the Fc portion of human IgG1 (PHveC-VhIg), we found that all of the transgenic founder mice showed a microphthalmia. The purpose of this study is to examine functions of the extracellular domains of nectin-1 in eye development using transgenic technology.


METHODS
Eyes of four different transgenic mouse lines expressing each soluble form of nectin-1 were analyzed histologically. Tissue sections were processed with hematoxylin-eosin staining and indirect immunoperoxidase technique.


RESULTS
All of five transgenic mouse founders expressing PHveC-VhIg, and of three lines expressing PHveC-VpIg made of the first Ig-like domain fused to porcine Fc portions at 5 weeks showed a microphthalmia, but not all of the transgenic mouse lines expressing PHveCIg or PHveCpIg made of the entire ectodomain fused to human or porcine Fc portions. In the abnormal eyes, the vitreous body was almost absent. In PHveC-VhIg-expressing mice at postnatal day 6, each vitreous space was very small. In the neonatal transgenic mice, the vitreous body was almost the same as that of control mice, and PHveC-VhIg was expressed in the optic nerve, conjunctival epithelium, ciliary body, corneal and lens epithelium. At this stage, nectin-1, -3 and -4 were stained in the optic nerve of control mice as well as in that of the transgenic mice. Nectin-1 is faintly stained in the epithelium of the cornea and lens epithelium, but not in the ciliary body.


CONCLUSIONS
Soluble forms of the first Ig-like domain of nectin-1 (PHveC-VhIg and PHveC-VpIg), but not those of the entire ectodomain (PHveCIg and PHveCpIg), lead to microphthalmia and lack of vitreous body in the transgenic mice.
Yoshida
Kazuhiko
K
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo 060-8638, Japan.
Tomioka
Yukiko
Y
Kase
Satoru
S
Morimatsu
Masami
M
Shinya
Kyoko
K
Ohno
Shigeaki
S
Ono
Etsuro
E
D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005822:Genetic Vectors; D007124:Immunoenzyme Techniques; D007136:Immunoglobulins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000075983:Nectins; D009898:Optic Disk / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins; D014822:Vitreous Body / Q000002:abnormalities* / Q000473:pathology
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D011993:Recombinant Fusion Proteins