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Samir S. Deeb, Darren Bisset, Maria N. Pavlova, Ding-Geng Chen; Regulation of Retinal Gene Expression by Thyroid Hormone and it Receptors During Mouse Development. Invest. Ophthalmol. Vis. Sci. 2011;52(14):54.
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To identify all retinal genes that are controlled by thyroid hormone (TH) via thyroid hormone receptors alpha (Tra) and beta 2 (Trb2) during mouse development.
Microarray samples were prepared using RNA isolated from mouse retinas at P10 and resulted microarray data were analyzed using R/Bioconductor. Many of significant results were validated by quantitative RT-PCR. Neural retina leucine zipper gene knockout (Nrl-/-) mice, with predominant cones photoreceptors, were used in these experiments. To identify genes regulated by TH, we compared retinal gene expression between control and hypothyroid Nrl-/- postnatal day 10 (P10) pups. Hypothyroidism was accomplished by treatment with Methimazole (MMI) starting at embryonic stage 14. In order to identify genes regulated by Trb, we generated an Nrl-/--Trb2-/- double knockout strain and compared its retinal gene expression at P10 with the Nrl-/- strain as a control.
Reducing the level of TH levels in Nrl-/- to about 25% by treatment with MMI resulted in a statistically significant decrease in a number of cone photoreceptor mRNA levels. These include green opsin (Opn1MW), hairless, Kruppel-like factor 9, Arrestin 3, Guanylate cyclase activator1B, retbindin, retinoschisis 1, G-protein-coupled receptor kinase 1, retinol dehydrogenase 12 and Trb. Reversibly, an increase in the levels of mRNA of cadherin 23, doublecortin-like kinase and adrenergic receptor beta 2 gene transcripts was observed. Knockout of Trb2 resulted in significant down regulation of only the Opn1MW gene.
Thyroid hormone regulates a large number of genes during retinal development, most likely via the Tra1 and Tra2 receptors. The Trb2 receptor, which is critical for differentiation of the green cones in mice, induces expression of only Opn1MW.
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