Meckelin 3 is necessary for photoreceptor outer segment development in rat Meckel syndrome.
Meckelin 3 is necessary for photoreceptor outer segment development in rat Meckel syndrome.
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DOI：
10.1371/journal.pone.0059306
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Belecky-Adams TL
中科院分区：
文献类型：
--
作者：
Tiwari S;Hudson S;Gattone VH 2nd;Miller C;Chernoff EA;Belecky-Adams TL
纤毛疾病会导致多器官病变，包括肾囊肿、耳聋、肥胖和视网膜退化。视网膜光感受器具有连接内外段的纤毛，负责分子的运输，以发展和维持外段过程。本研究采用免疫组织化学、细胞死亡分析和电子显微镜等方法，研究了Meckelin(MKS3)在Wistar多囊肾病WPK/WPK大鼠光感受器发育和存活过程中的表达。在出生后第10天(第10天)和第21天，MKS3在整个视网膜都有表达。然而，在成熟的视网膜中，MKS3的表达仅限于光感受器和视网膜神经节细胞层。在P10时，野生型和纯合子WPK突变型视网膜都具有所有的视网膜细胞类型。相反，到了P21，表达视杆细胞和视锥细胞特异性标记的细胞数量较少，而且Opsins的表达似乎异常地定位于细胞体。细胞死亡分析与光感受器特异性标志物的消失一致，表明细胞正在经历caspase依赖的细胞死亡。在电子显微镜下，P10光感受器显示出带有轴丝的不发育的外节段，但没有形成与野生型对应的明显存在的外节段盘。在p21，突变型外节与P10突变型外节基本相同，只有一个短的轴丝，而野生型对照已经发育出具有许多排列整齐的圆盘的外节。我们认为，MKS3对于连接纤毛和发育的外段的形成并不重要，但对于外段突起的成熟是至关重要的。
Ciliopathies lead to multiorgan pathologies that include renal cysts, deafness, obesity and retinal degeneration. Retinal photoreceptors have connecting cilia joining the inner and outer segment that are responsible for transport of molecules to develop and maintain the outer segment process. The present study evaluated meckelin (MKS3) expression during outer segment genesis and determined the consequences of mutant meckelin on photoreceptor development and survival in Wistar polycystic kidney disease Wpk/Wpk rat using immunohistochemistry, analysis of cell death and electron microscopy. MKS3 was ubiquitously expressed throughout the retina at postnatal day 10 (P10) and P21. However, in the mature retina, MKS3 expression was restricted to photoreceptors and the retinal ganglion cell layer. At P10, both the wild type and homozygous Wpk mutant retina had all retinal cell types. In contrast, by P21, cells expressing rod- and cone-specific markers were fewer in number and expression of opsins appeared to be abnormally localized to the cell body. Cell death analyses were consistent with the disappearance of photoreceptor-specific markers and showed that the cells were undergoing caspase-dependent cell death. By electron microscopy, P10 photoreceptors showed rudimentary outer segments with an axoneme, but did not develop outer segment discs that were clearly present in the wild type counterpart. At p21 the mutant outer segments appeared much the same as the P10 mutant outer segments with only a short axoneme, while the wild-type controls had developed outer segments with many well-organized discs. We conclude that MKS3 is not important for formation of connecting cilium and rudimentary outer segments, but is critical for the maturation of outer segment processes.
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DOI：
10.1083/jcb.200806009
发表时间：
2008-11-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Baker SA;Haeri M;Yoo P;Gospe SM 3rd;Skiba NP;Knox BE;Arshavsky VY
通讯作者：
Arshavsky VY
影响因子：
15.9
作者：
Boldt, Karsten;Mans, Dorus A.;Ueffing, Marius
通讯作者：
Ueffing, Marius
影响因子：
3.5
作者：
Estrada-Cuzcano, Alejandro;Roepman, Ronald;Mans, Dorus A.
通讯作者：
Mans, Dorus A.
DOI：
10.1073/pnas.072557799
发表时间：
2002-04-16
影响因子：
11.1
作者：
Alfinito, PD;Townes-Anderson, E
通讯作者：
Townes-Anderson, E
影响因子：
9.8
作者：
Baala, Lekbir;Romano, Stephane;Attie-Bitach, Tania
通讯作者：
Attie-Bitach, Tania