Transgenic mice expressing a constitutively active retinoic acid receptor in the lens exhibit ocular defects.
Retinoic acid receptors (RARs) modulate gene expression following association with retinoic acid (RA). In transient transfection, an RAR alpha-beta-galactosidase fusion protein (RAR-LacZ) was able to transactivate expression in the absence of RA. When expressed in the ocular lens of transgenic mice, this constitutively active RAR-LacZ fusion gene resulted in founder and progeny animals that exhibited cataracts and microphthalmia, both being characteristics of retinoid-induced teratogenesis. The transgenic phenotypes indicate that retinoid teratogenesis can be mimicked by expression of a constitutively active RAR-LacZ fusion protein in retinoid-sensitive tissues.
Balkan
W
W
Department of Microbiology and Immunology, Duke University, Durham, North Carolina 27710.
Klintworth
G K
GK
Bock
C B
CB
Linney
E
E
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002386:Cataract / Q000151:congenital / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D007763:Lac Operon; D007908:Lens, Crystalline / Q000002:abnormalities* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D008850:Microphthalmos / Q000235:genetics; D008969:Molecular Sequence Data; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014212:Tretinoin / Q000633:toxicity*
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014212:Tretinoin