Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris in Tg737 mutant mice
Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris in Tg737 mutant mice
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DOI：
10.1046/j.1523-1755.2003.00863.x
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发表时间：
2003-04-01
影响因子：
19.6
通讯作者：
Murcia, NS
中科院分区：
文献类型：
--
作者：
Brown, NE;Murcia, NS
背景在Tg 737（orpk）（orpk）突变小鼠中观察到肾囊肿和肾小管上皮细胞上的纤毛缩短，表明囊肿发生和纤毛发生之间存在潜在联系。为了进一步检验这一假设，我们已经表征了orpk、orpk ; Tg 737 Rsq（orpk拯救）和Tg 737（Delta 2 -3betaGal）; Tg 737 Rsq（KO拯救）小鼠中囊性疾病和纤毛表达的进展。从出生后第0天（P）至P21（orpk突变体）或从P0至P210（orpk挽救和KO挽救动物）生成并分析了Orpk、orpk挽救和KO挽救动物。近端小管（PT）和集合小管（CT）通过免疫组化确定使用节段特异性凝集素和节段特异性囊性指数计算。扫描电镜观察orpk、orpk拯救和KO拯救动物包囊中纤毛的表达。KO拯救和orpk拯救动物发生成人发病常染色体隐性遗传性多囊肾病（ARPKD）。纤毛表达的超微结构分析显示orpk的包囊表达短纤毛，而KO拯救动物的包囊表达正常长度的纤毛，orpk拯救动物的包囊表达比野生型长2 - 5倍的纤毛。虽然这些数据与北极星在纤毛发生中的作用是一致的，但它不支持纤毛发生和囊性疾病之间的直接联系。与这些ARPKD小鼠模型相关的囊肿形成的相似性和纤毛表达的显著差异表明，囊肿形成和纤毛表达是由北极星调控的独立表型特征。
Background. Renal cysts and shortened cilia on renal tubular epithelia have been observed in Tg737(orpk) (orpk ) mutant mice, suggesting a potential connection between cystogenesis and ciliogenesis. To further test this hypothesis we have characterized the progression of cystic disease and cilia expression in orpk , orpk ;Tg737Rsq (orpk rescue), and Tg737(Delta2-3betaGal) ;Tg737Rsq (KO rescue) mice.Methods. Orpk , orpk rescue, and KO rescue animals were generated and analyzed from postnatal day (P) 0 to P21 (orpk mutants) or from P0 to P210 (orpk rescue and KO rescue animals). Proximal tubules (PT) and collecting tubules (CT) were identified by immunohistochemistry using segment-specific lectins and a segment-specific cystic index was calculated. Scanning electron microscopy was utilized to observe and measure cilia expression in cysts from orpk , orpk rescue, and KO rescue animals.Results. KO rescue and orpk rescue animals develop adult-onset autosomal-recessive polycystic kidney disease (ARPKD). Ultrastructural analysis of cilia expression revealed that cysts from orpk expressed short cilia, whereas cysts from KO rescue animals expressed normal length cilia and cysts from orpk rescue animals expressed cilia that are two to five times longer than wild type.Conclusion. While this data is consistent with a role for polaris in ciliogenesis, it does not support a direct connection between ciliogenesis and cystic disease. Similarities in cyst formation and striking differences in cilia expression associated with these ARPKD mouse models indicates that cyst formation and cilia expression are independent phenotypic features regulated by polaris.