The pink-eyed dilution locus controls the biogenesis of melanosomes and levels of melanosomal proteins in the eye
The pink-eyed dilution locus controls the biogenesis of melanosomes and levels of melanosomal proteins in the eye
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DOI：
10.1006/exer.1998.0599
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发表时间：
1999-02-01
影响因子：
3.4
通讯作者：
Brilliant, MH
中科院分区：
文献类型：
--
作者：
Orlow, SJ;Brilliant, MH
已知红眼稀释（p）基因座控制眼睛中黑色素细胞和视网膜色素上皮（RPE）内产生的黑色素的量。我们已经研究了几种突变等位基因组合在小鼠p基因座上的脉络膜黑素细胞和RPE细胞中的黑素体的数量和形态以及已知存在于黑素体内的四种蛋白质的水平的影响：酪氨酸酶，酪氨酸酶相关蛋白1和2（TRP-1和TRP-2）和溶酶体相关膜蛋白-1（LAMP-1）。通过电子显微镜，我们观察到p（bx）/p（J）小鼠脉络膜黑色素体的大小和数量适度减少，但与野生型P/P小鼠相比，RPE的减少更为显著。相比之下。在p（un）/p（un）和p（6 H）/p（cp）小鼠的脉络膜和RPE中存在黑素体大小和数量的急剧减少，并且在p（6 H）/p（cp）小鼠的RPE中，基本上检测不到黑素体。在野生型小鼠中，酪氨酸酶水平。TRP-1和TRP-2在出生时表达较高，在10-14日龄时显示第二个表达高峰。42天后下降到无法检测的水平。所有三种突变等位基因组合都降低了这些黑素体蛋白的水平，其影响的相对严重程度为p（6 H）/p（cp）> p（un）/p（un）> p（bx）/p（J）。在无效p（6 H）/p（cp）小鼠中，这些蛋白的水平在出生时极低，没有观察到出生后的峰值，并且水平在14天下降到检测不到。在野生型小鼠中LAMP-1的水平最初上升，然后下降，而在突变小鼠中。水平从出生开始逐渐下降。在21日龄时，在每个突变体中观察到比野生型小鼠更高水平的LAMP-1。我们的研究结果表明，在p位点的突变影响黑素体的大小，数量，形状和内容。暗示p基因产物参与了这个细胞器的正常生物发生。(C)北京：科学出版社.
The pink-eyed dilution (p) locus is known to control the quantity of melanin pigment made within melanocytes and retinal pigment epithelium (RPE) in the eye. We have examined the effects of several mutant allele combinations at the murine p locus on the number and morphology of melanosomes in choroidai melanocytes and RPE cells as well as on the levels of four proteins known to be present within melanosomes: tyrosinase, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2) and lysosome associated membrane protein-1 (LAMP-1). By electron microscopy, we observed a modest diminution in the size and number of choroidal melanosomes in p(bx)/p(J) mice but a more dramatic decrease in the RPE in comparison with wild-type P/P mice. By contrast. a drastic reduction in melanosome size and number was present in the choroid and RPE of p(un)/p(un) and p(6H)/p(cp) mice, and in the RPE of p(6H)/p(cp) mice, melanosomes were essentially undetectable. In wild-type mice, levels of tyrosinase. TRP-1 and TRP-2 were high at birth and showed a second peak of expression at 10-14 days of age. declining to undetectable levels by 42 days. All three mutant allele combinations reduced the levels of these melanosomal proteins with the relative severity of effects being p(6H)/p(cp) > p(un)/p(un) > p(bx)/p(J) In the null p(6H)/p(cp) mice, levels of these proteins were extremely low at birth, no postnatal peak was observed, and levels declined to undetectable by 14 days. Levels of LAMP-1 in wild-type mice rose initially and then declined whereas in the mutant mice. levels decreased gradually from birth. Higher levels of LAMP-1 were observed in each of the mutants than in the wild-type mice at 21 days of age. Our results demonstrate that mutations at the p locus affect the size, number, shape and contents of melanosomes. implicating the p gene product in the normal biogenesis of this organelle. (C) 1999 Academic Press.