Retinoschisin expression and localization in rodent and humanpineal and consequences of mouse RS1 gene knockout

[摘要] Purpose: The pineal gland shares a common neuroectoderm origin withthe retina, and like the retina, regulates circadian rhythms throughmelatonin secretion. Recent expressed tag sequence (EST) analysis showedthat several gene mutations, including RS1, which cause retinaldegeneration, are also expressed in the pineal gland. Mutations inRS1 result in structural delamination of the neural retinal layers,leading to formation of schisis cavities in men affected with "X-linkedretinoschisis" (XLRS). In this study, we evaluated RS1 expression inthe rat and mouse as well as in human pineal and looked formorphological changes in the pineal of the RS1 knockout(RS1-/Y) mouse.Methods: We analyzed rat and mouse pineal for RS1 expression byNorthern blot and in situ hybridization. RS protein, synaptophysin,S-100, and GFAP localization in the pineal of rat and mouse and RSprotein in human pineal were evaluated immunohistochemically.Morphological studies were performed using transmission electronmicroscopy and light microscopy comparing wild-type to theRS1-/Y mouse.Results: RS1 expression was detected in RNA isolated from boththe pineal and retina as a single major band migrating at about 5.5 kbpin Northern blots. RS1 riboprobe in situ hybridization demonstratedmessage in rat and mouse pineal, and immunohistochemistry showed RSprotein in pinealocytes expressing synaptophysin but not in interstitialGFAP- and S100-positive glial cells. RS protein was present in manypinealocytes in human pineal. In light and electron microscopicexamination of the pineal gland from RS1-/Y mice none of thestructural changes found in the retina, such as cavity formation andloosening of the tissue, were seen.Conclusions: This study demonstrates that RS protein is expressed inthe pinealocytes but not in interstitial glial cells. The lack ofstructural abnormalities in the RS1-/Y mice suggests that RSserves a different function in the pineal gland than in the retina.

[学科分类] 生物化学/生物物理