PURPOSE: To determine the functional contribution of retinoic acid receptor (RAR)-alpha in the developing murine neural retina, through a phenotypic analysis of the corresponding null mutants. METHODS: RARalpha mutant (Rara(-/-)) mice were compared with wild-type littermates at several stages of pre- and postnatal development. An RA-response element (RARE)-containing reporter transgene was used to assess the contribution of RARalpha to retinoid signaling in the retina. In situ hybridization was performed on serial eye sections to investigate the expression of main developmental regulators. Immunofluorescence was used to detect differentiated cell types in the adult retina. Mutants were also subjected to clinical observation and visual function evaluation with the optomotor test and electroretinography. RESULTS: Both isoform transcripts of RARalpha were expressed throughout the neural retina at various stages of pre- and postnatal development. In the Rara(-/-) mice the RARE-reporter transgene consistently failed to activate in the developing neural retina. However, they did not exhibit any alteration of the expression patterns of molecular determinants and had a normal organization of retinal cell types at postnatal stages. Their performance in visual tests was indistinguishable from that of control littermates. CONCLUSIONS: Although RARalpha mediates RARE reporter transgene activity in the neural retina, its function is not necessary for the retina to develop and function normally. These data suggest that retinoic acid regulates neural retinal development through other, possibly RAR-independent, pathways.
PURPOSE: To determine the functional contribution of retinoic acid receptor (RAR)-alpha in the developing murine neural retina, through a phenotypic analysis of the corresponding null mutants. METHODS:RARalpha mutant (Rara(-/-)) mice were compared with wild-type littermates at several stages of pre- and postnatal development. An RA-response element (RARE)-containing reporter transgene was used to assess the contribution of RARalpha to retinoid signaling in the retina. In situ hybridization was performed on serial eye sections to investigate the expression of main developmental regulators. Immunofluorescence was used to detect differentiated cell types in the adult retina. Mutants were also subjected to clinical observation and visual function evaluation with the optomotor test and electroretinography. RESULTS: Both isoform transcripts of RARalpha were expressed throughout the neural retina at various stages of pre- and postnatal development. In the Rara(-/-) mice the RARE-reporter transgene consistently failed to activate in the developing neural retina. However, they did not exhibit any alteration of the expression patterns of molecular determinants and had a normal organization of retinal cell types at postnatal stages. Their performance in visual tests was indistinguishable from that of control littermates. CONCLUSIONS: Although RARalpha mediates RARE reporter transgene activity in the neural retina, its function is not necessary for the retina to develop and function normally. These data suggest that retinoic acid regulates neural retinal development through other, possibly RAR-independent, pathways.