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1 From the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan; and the 2 Japan Science and Technology Corporation (CREST), Saitama, Japan.
PURPOSE. To clarify the functions of a specific subtype of thyroid hormone receptor (TR), TRß2, and photoreceptor cellspecific nuclear receptor (PNR) in the development of cone photoreceptors.
METHODS. The expression of short (S)- and medium (M)-wavelength cone opsins was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis in mice without a functional PNR (rd7/rd7 mice), and levels of plasma thyroid hormones and expression of TRß2 were also examined. Concomitantly, by means of reporter assays, the roles of PNR and TRß2 in the S- and M-cone opsin expression were explored at the transcriptional level.
RESULTS. In rd7/rd7 mice, an abnormal increase in cone photoreceptors was observed immediately before retinal maturation normally occurs. Although an increase in S-cone opsin in the retina was observed during and after retinal development, the expression of M-cone opsin expression was not perturbed during retinal maturation. Plasma concentrations of thyroid hormone and levels of TRß2 expression in the rd7/rd7 mouse retina over the developmental period were normal. Transcriptional studies demonstrated that TRß2, but not PNR, activated the M-cone opsin gene promoter function, while suppressing the S-cone opsin promoter function enhanced by CRX in a thyroid hormonedependent manner.
CONCLUSIONS. The results indicate that PNR may suppress proliferation of cone photoreceptor progenitor cells and that the regulation of S- and M-cone opsin gene expression is mediated by TRß2 and CRX, but not by PNR. Thus, our results partly disclosed the molecular mechanism of cone photoreceptor development, highlighting the distinct functions of PNR and TRß2.
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