Rx is expressed in mouse embryos at E7.5 in the presumptive forebrain and becomes restricted to the developing retina, posterior pituitary and hypothalamus. Deletion of the Rx gene revealed that it is required for the formation of these structures, as its loss causes anophthalmia and ventral neural tube defects. Recently, Rx has also been shown to be active in the adult mouse and human neural retina (V. Voronina and P. Mathers, unpublished). To determine the role of Rx in adult retina physiology, we are performing conditional knockouts of the gene after retinogenesis is complete. To achieve this, we have produced mice that carry a floxed Rx gene so that normal Rx function can be disrupted by Cre-mediated recombination. We are using two independent approaches to specifically target Cre-recombination to floxed-Rx mice. The first will induce Cre expression in the retina (and elsewhere) of adult mice using a cre transgene that is inducible by tamoxifen. This global expression should only affect the retina, as Rx is not expressed in other adult tissues. In the second approach, we are specifically deleting Rx in a subset of retinal cells (photoreceptors) by placing cre under the control of the opsin promoter. These two strategies for the deletion of adult Rx gene function will provide a model for two common causes of blindness, retinal dystrophy and retinal degeneration.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010339-02
Application #
6559222
Study Section
(CDBL)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Waters, Samuel T; Wilson, Catherine P; Lewandoski, Mark (2003) Cloning and embryonic expression analysis of the mouse Gbx1 gene. Gene Expr Patterns 3:313-7
Kim, Yong-Sik; Nakanishi, Gen; Lewandoski, Mark et al. (2003) GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions. Nucleic Acids Res 31:5513-25