Phosphodiesterase 6β Expression In Developing Mouse Retina.
Phosphodiesterase 6β Expression In Developing Mouse Retina.
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发表时间：
2015
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通讯作者：
Fadi Assaf;Ju Zhang;J. Ogilvie
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作者：
Fadi Assaf;Ju Zhang;J. Ogilvie
rd1 小鼠是经过充分研究的视网膜色素变性 (RP) 模型，这是一种遗传性视网膜退行性疾病，大约每 4000 人中就有 1 人受到影响。其特征是编码磷酸二酯酶 6β (PDE6β) 的 Pde6b 基因发生突变，磷酸二酯酶 6β 是光转导的下游效应子。 Pde6b 基因表达发生在胚胎时期的小鼠视网膜中，而参与光转导的其他蛋白质则在出生后第 5 天 (P5) 左右表达。本研究的主要目的是研究光感受器发育过程中 PDE6β 蛋白的时空表达模式。使用来自 P2 - P21 的野生型和 rd1 小鼠视网膜的蛋白质印迹，我们证明 PDE6β 蛋白在 P2 的野生型视网膜中表达，并且在 rd1 视网膜中未检测到。免疫组织化学最早在野生型视网膜中检测到 PDE6β 是在 P6，此时它仅限于感光层的顶端区域。 PDE6β蛋白在光感受器细胞分化之前和在其他光转导蛋白表达之前的表达与PDE6β可能在光感受器发育过程中发挥不同于其在光转导中的作用的假设是一致的。我们的实验室之前表明，异戊二烯化 Rab 受体 1 (PRA1)（一种囊泡运输蛋白）在发育中的 rd1 视网膜中下调，尽管其在视网膜中的功能尚不清楚。本研究的第二个目的是探讨 PRA1 和 PDE6β 之间的关系。我们使用免疫组织化学来确定这两种蛋白在出生后分化期间是否共定位。然而，没有检测到 PDE6β 和 PRA1 之间的共定位。 PRA1 在视网膜发育中的功能仍有待阐明。
The rd1 mouse is a well-studied model of retinitis pigmentosa (RP), an inherited retinal degenerative disease affecting approximately 1 in 4000 people. It is characterized by a mutation in the Pde6b gene that codes for Phosphodiesterase 6β (PDE6β), a downstream effector of phototransduction. Pde6b gene expression occurs embryonically in mouse retina, whereas other proteins involved in phototransduction are expressed around postnatal day 5 (P5). The primary aim of this study is to investigate the temporal and spatial expression pattern of PDE6β protein during photoreceptor development. Using Western blots with wild type and rd1 mouse retinas from P2 - P21 we demonstrated that PDE6β protein is expressed in wild type retinas by P2 and is not detected in rd1 retinas. The earliest detection of PDE6β in wild type retinas by immunohistochemistry was at P6, where it was confined to the apical region of the photoreceptor layer. The expression of PDE6β protein prior to differentiation of photoreceptor cells and prior to expression of other phototransduction proteins is consistent with the hypothesis that PDE6β may play a role during photoreceptor development distinct from its role in phototransduction. Our lab previously showed that Prenylated Rab Acceptor 1 (PRA1), a vesicular trafficking protein, is downregulated in the developing rd1 retina, although its function in the retina is unknown. The second aim of this study was to explore the relationship between PRA1 and PDE6β. We used immunohistochemistry to determine whether the two proteins are co-localized during the postnatal differentiation period. However, no co-localization between PDE6β and PRA1 was detected. The function of PRA1 in developing retina remains to be elucidated.