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Anika Glaschke, Martin Glösmann, Leo Peichl; Developmental Changes of Cone Opsin Expression but Not Retinal Morphology in the Hypothyroid Pax8 Knockout Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(3):1719-1727. doi: 10.1167/iovs.09-3592.
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The effects of postnatal hypothyroidism on retinal development and spatial patterning of cone opsin expression were studied in Pax8-deficient mice. Pax8−/− mice are incapable of synthesizing thyroxine and serve as a model for congenital hypothyroidism.
Pax8−/−, Pax8+/−, and Pax8+/+ littermates were studied. Serum thyroid hormone levels, body weight, and eye size were measured. Retinal cell-type–specific antibodies were used on frozen sections to examine the postnatal development of the major retinal cell classes and of retinal structure. The expression of short-wavelength–sensitive (S) and middle-to-long-wavelength–sensitive (M) cone opsins was assessed with opsin antibodies on retinal sections and whole retinas. The pattern of S opsin mRNA was assessed by in situ hybridization.
In Pax8−/− mice, S opsin was upregulated in all cones, whereas M opsin was downregulated throughout the retina, the wild-type dorsoventral gradients of S and M opsin expression were absent. Otherwise, Pax8−/− mice showed no overt mutant phenotype in eye size, gross retinal anatomy, and the time-course of structural differentiation of retinal photoreceptors, horizontal cells, bipolars, amacrines, ganglion cells, and Müller glia cells.
Pax8−/− mice show a pattern of cone opsin expression that differs substantially from the wild-type pattern, but exhibit no apparent alterations in general retinal development. The finding that a postnatal decrease in serum thyroid hormone yields changes in postnatal cone opsin expression is consistent with a ligand-dependent role of thyroid hormone receptor β2 in S opsin repression and M opsin activation.
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