Ivanchuk S M, Myers S M, Mulligan L M
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Oncogene. 1998 Feb 26;16(8):991-6. doi: 10.1038/sj.onc.1201622.
The mature mammalian kidney arises through a series of reciprocal inductive interactions between two different cell groups, the ureteric bud epithelium and the metanephric mesenchyme. The RET receptor tyrosine kinase is required for induction and development of the metanephric kidney. Differential splicing at the 3' end of RET results in transcripts encoding three isoforms that differ with respect to their C-terminal 9 (RET9), 51 (RET51) or 43 (RET43) amino acids. In vitro assays have identified differences in the abilities of the RET9 and RET51 isoforms to induce differentiation suggesting functional differences between these proteins. We examined the relative expression levels of the three RET 3' splicing variants in developing human kidney using semi-quantitative RT-PCR. We observed consistent expression of the RET9 and RET43 variants in kidney samples spanning 7.5 through 24 weeks gestation. At early gestational ages (7.5-8.5 weeks), RET51 expression was very low (+/-5%) compared to RET9; however, a rapid seven fold increase in expression was detected by 9 weeks. Our data suggest that RET51 may contribute to differentiation-related events occurring after 8.5 weeks gestation rather than to induction of the human kidney.
成熟的哺乳动物肾脏是通过输尿管芽上皮和后肾间充质这两种不同细胞群之间一系列相互诱导的相互作用而形成的。RET受体酪氨酸激酶是后肾发育和诱导所必需的。RET在3'端的可变剪接产生了三种转录本，分别编码C末端含有9个氨基酸（RET9）、51个氨基酸（RET51）或43个氨基酸（RET43）的三种异构体。体外实验已确定RET9和RET51异构体在诱导分化能力上存在差异，这表明这些蛋白质之间存在功能差异。我们使用半定量RT-PCR检测了发育中的人类肾脏中三种RET 3'剪接变体的相对表达水平。我们观察到，在妊娠7.5周至24周的肾脏样本中，RET9和RET43变体表达一致。在妊娠早期（7.5 - 8.5周），与RET9相比，RET51的表达非常低（±5%）；然而，到9周时，其表达迅速增加了7倍。我们的数据表明，RET51可能有助于妊娠8.5周后发生的与分化相关的事件，而不是人类肾脏的诱导。
