UCL Institute of Child Health, London, UK.
Pediatr Nephrol. 2012 Jun;27(6):991-8. doi: 10.1007/s00467-012-2100-5. Epub 2011 Oct 13.
Fraser syndrome (FS) features renal agenesis and cystic kidneys. Mutations of FRAS1 (Fraser syndrome 1)and FREM2 (FRAS1-related extracellular matrix protein 2)cause FS. They code for basement membrane proteins expressed in metanephric epithelia where they mediate epithelial/mesenchymal signalling. Little is known about whether and where these molecules are expressed in more mature kidneys.
In healthy and congenital polycystic kidney (cpk)mouse kidneys we sought Frem2 expression using a LacZ reporter gene and quantified Fras family transcripts. Fras1 immunohistochemistry was undertaken in cystic kidneys from cpk mice and PCK (Pkhd1 mutant) rats (models of autosomal recessive polycystic kidney disease) and in wildtype metanephroi rendered cystic by dexamethasone.
Nascent nephrons transiently expressed Frem2 in both tubule and podocyte epithelia. Maturing and adult collecting ducts also expressed Frem2. Frem2 was expressed in cpk cystic epithelia although Frem2 haploinsufficiency did not significantly modify cystogenesis in vivo. Fras1 transcripts were significantly upregulated, and Frem3 downregulated, in polycystic kidneys versus the non-cystic kidneys of littermates. Fras1 was immunodetected in cpk, PCK and dexamethasone-induced cystepithelia.
These descriptive results are consistent with the hypothesis that Fras family molecules play diverse roles in kidney epithelia. In future, this should be tested by conditional deletion of FS genes in nephron segments and collecting ducts.
弗雷泽综合征（FS）的特征是肾发育不全和囊性肾脏。FRAS1（Fraser 综合征 1）和 FREM2（FRAS1 相关细胞外基质蛋白 2）的突变导致 FS。它们编码在后肾上皮中表达的基膜蛋白，在那里它们介导上皮/间充质信号转导。关于这些分子是否以及在何处表达在更成熟的肾脏中，知之甚少。
在健康和先天性多囊肾病（cpk）小鼠肾脏中，我们使用 LacZ 报告基因寻找 Frem2 的表达，并定量 Fras 家族转录本。在 cpk 小鼠和 PCK（Pkhd1 突变）大鼠（常染色体隐性多囊肾病的模型）的囊性肾脏中进行 Fras1 免疫组织化学染色，并在 dexamethasone 致囊性的野生型后肾中进行 Fras1 免疫组织化学染色。
新生肾单位在肾小管和足细胞上皮中瞬时表达 Frem2。成熟和成年集合管也表达 Frem2。Frem2 在 cpk 囊性上皮中表达，尽管 Frem2 单倍不足在体内并没有显著改变囊肿的发生。与同窝对照非囊性肾脏相比，多囊肾病中的 Fras1 转录本显著上调，而 Frem3 下调。在 cpk、PCK 和 dexamethasone 诱导的囊性上皮中检测到 Fras1。
这些描述性结果与 Fras 家族分子在肾脏上皮中发挥多种作用的假说一致。将来，应该通过在肾单位和集合管中条件性缺失 FS 基因来测试这一假说。
