The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation.
The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation.
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DOI：
10.1016/j.exer.2018.02.001
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发表时间：
2018-04
影响因子：
3.4
通讯作者：
Wistow G
中科院分区：
文献类型：
--
作者：
Fan J;Lerner J;Wyatt MK;Cai P;Peterson K;Dong L;Wistow G
KLPH/lctl 属于 Klotho 蛋白质家族。表达序列标签分析出乎意料地揭示，KLPH 在眼晶状体中高表达，而 Northern 印迹显示，在眼中的表达比在其他组织中高得多。小鼠的原位杂交将 mRNA 定位到晶状体，特别是赤道上皮。免疫荧光检测到晶状体上皮细胞中的 KLPH 在萌发/分化区的水平最高。通过同源重组删除小鼠中的 KLPH 基因。在广泛的病理学检查中对同窝基因敲除（KO）和野生型（WT）小鼠进行了比较，结果均非常正常，没有显示出缺失的全身影响。然而，年轻时晶状体虽然表面上正常，但存在聚焦缺陷，并通过裂隙灯检查显示出与年龄相关的皮质白内障。全晶状体成像显示，KO 小鼠晶状体缝合线杂乱，形成松散的双 y 或 x，而不是 WT 紧密的 y 结构。 KO 和 WT 同窝小鼠的 RNA 测序图谱证实，KO 晶状体中不存在 KLPH mRNA，并且还显示完全不存在 Clic5 转录本，Clic5 是一种与小鼠模型中纤毛/基体相关听觉缺陷相关的蛋白质。晶状体上皮平片的免疫荧光显示 Clic5 定位于纤毛/中心体。 Clic5（jitterbug）突变小鼠的缝合线也有缺陷。这些结果表明 KLPH 是 Clic5 晶状体特异性表达所必需的，并且 Clic5 在控制晶状体纤维细胞延伸和组织的机制中具有重要作用。
KLPH/lctl belongs to the Klotho family of proteins. Expressed sequence tag analyses unexpectedly revealed that KLPH is highly expressed in the eye lens while northern blots showed that expression is much higher in the eye than in other tissues. In situ hybridization in mouse localized mRNA to the lens, particularly in the equatorial epithelium. Immunofluorescence detected KLPH in lens epithelial cells with highest levels in the germinative/differentiation zone. The gene for KLPH in mouse was deleted by homologous recombination. Littermate knockout (KO) and wild type (WT) mice were compared in a wide panel of pathology examinations and were all grossly normal, showing no systemic effects of the deletion. However, the lens, while superficially normal at young ages, had focusing defects and exhibited age-related cortical cataract by slit lamp examination. Whole-lens imaging showed that KO mice had disorganized lens sutures, forming a loose double-y or x instead of the tight y formation of WT. RNA-seq profiles for KO and WT littermates confirmed the absence of KLPH mRNA in KO lens and also showed complete absence of transcripts for Clic5, a protein associated with cilium/basal body related auditory defects in a mouse model. Immunofluorescence of lens epithelial flat mounts showed that Clic5 localized to cilia/centrosomes. Mice mutant for Clic5 (jitterbug) also had defective sutures. These results suggest that KLPH is required for lens-specific expression of Clic5 and that Clic5 has an important role in the machinery that controls lens fiber cell extension and organization.
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影响因子：
2.7
作者：
Chen, Yongjuan;Stump, Richard J. W.;Lovicu, Frank J.;Shimono, Akihiko;McAvoy, John W.
通讯作者：
McAvoy, John W.
影响因子：
2.7
作者：
Dawes, L. J.;Sugiyama, Y.;Lovicu, F. J.;Harris, C. G.;Shelley, E. J.;McAvoy, J. W.
通讯作者：
McAvoy, J. W.
影响因子：
5.3
作者：
Gagnon, Leona H.;Longo-Guess, Chantal M.;Johnson, Kenneth R.
通讯作者：
Johnson, Kenneth R.
影响因子：
3.4
作者：
Audette, Dylan S.;Scheiblin, David A.;Duncan, Melinda K.
通讯作者：
Duncan, Melinda K.
DOI：
10.1007/978-1-61779-510-7_12
发表时间：
2012
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Sugiyama, Yuki;McAvoy, John W
通讯作者：
McAvoy, John W