Retinoic acid receptor (RAR)-alpha is not critically required for mediating retinoic acid effects in the developing mouse retina.
OBJECTIVE
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.
Cammas
Laura
L
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 10142 Illkirch, France.
Trensz
Frédéric
F
Jellali
Abdeljalil
A
Ghyselinck
Norbert B
NB
Roux
Michel J
MJ
Dollé
Pascal
P
D000818:Animals; D002454:Cell Differentiation; D004596:Electroretinography; D047108:Embryonic Development / Q000502:physiology; D005451:Fluorescein Angiography; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology; D017930:Genes, Reporter; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity; D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D020218:Response Elements; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000502:physiology*
D020033:Protein Isoforms; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin