| First Author | Grondona JM | Year | 1996 |
| Journal | Development | Volume | 122 |
| Issue | 7 | Pages | 2173-88 |
| PubMed ID | 8681798 | Mgi Jnum | J:34183 |
| Mgi Id | MGI:81656 | Doi | 10.1242/dev.122.7.2173 |
| Citation | Grondona JM, et al. (1996) Retinal dysplasia and degeneration in RARbeta2/RARgamma2 compound mutant mice. Development 122(7):2173-88 |
| abstractText | The eye is the organ whose development is the most frequently altered in response to maternal vitamin A deficiency [VAD; Warkany, J. and Schraffenberger, S. (1946). Archs Ophthalmol. 35, 150-169]. With the exception of prenatal retinal dysplasia, all the ocular abnormalities of the fetal VAD syndrome are recapitulated in mouse mutants lacking either RAR alpha and RAR beta 2, RAR alpha and RAR gamma, RAR gamma and RAR beta 2 or RXR alpha [Lohnes, D., Mark, M., Mendelsohn, C., Dolle, P., Dierich, A., Gorry, P., Gansmuller, A. and Chambon, P. (1994) Development 120, 2723-2748; Mendelsohn, C., Lohnes, D. Decimo, D., Lufkin, T., LeMeur, M., Chambon, P. and Mark, M. (1994) Development 120, 2749-2771; Kastner, P., Grondona, J. Mark, M., Gansmuller, A., LeMeur, M., Decimo, D., Vonesch, J.L., Dolle, P. and Chambon, P. (1994) Cell 78, 987-1003], thus demonstrating that retinoic acid (RA) is the active vitamin A metabolite during prenatal eye morphogenesis. Whether retinoids are also involved in postnatal eye development could not be investigated, as VAD newborns are not viable and the above RAR double null mutants and RXR alpha null mutants died in utero or at birth. We report here the generation of viable RAR beta 2/ RAR gamma 2 double null mutant mice, which exhibit several eye defects. The neural retina of newborn RAR beta 2 gamma 2 mutants is thinner than normal due to a reduced rate of cell proliferation, and from day 4 shows multiple foci of disorganization of its layers. These RAR beta 2 gamma 2 mutants represent the first genetically characterized model of retinal dysplasia and their phenotype demonstrates that RARs, and therefore RA, are required for retinal histogenesis. The RAR beta 2 gamma 2 retinal pigment epithelium (RPE) cells display histological and/or ultrastructural alterations and/or fail to express cellular retinol binding protein I(CRBPI). Taken altogether, the early onset of the RPE histological defects and their striking colocalisation with areas of the neural retina displaying a faulty laminar organization, a reduced neuroblastic proliferation, and a lack of photoreceptor differentiation and/or increased apoptosis, make the RPE a likely target tissue of the RAR beta 2 gamma 2 double null mutation. A degeneration of the adult neural retina, which may similarly be secondary to a defective RPE, is also observed in these mutants, thus demonstrating an essential role of RA in the survival of retinal cells. Moreover, all RAR beta 2 gamma 2 mutants display defects in structures derived from the periocular mesenchyme including local agenesis of the choroid and of the sclera, small eyelids, and a persistence of the primary mesenchymal vitreous body. A majority of the RAR beta 2 single null mutants also exhibit this latter defect, thus demonstrating that the RAR beta 2 isoform plays a unique role in the formation of the definitive vitreous body. |
