Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation
Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation
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DOI：
10.1016/s0092-8674(01)00453-6
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发表时间：
2001-08-10
期刊：
影响因子：
64.5
通讯作者：
Schedl, A
中科院分区：
文献类型：
--
作者：
Hammes, A;Guo, JK;Schedl, A
Wt 1的选择性剪接导致在锌指3和4之间插入或省略三个氨基酸KTS。体外实验表明，不同的分子功能+和-KTS亚型。我们已经产生了小鼠品系，其中特定的同种型已经被去除。具有+KTS水平降低的杂合子小鼠发展成肾小球硬化，并且代表Frasier综合征的模型。这两种菌株的纯合突变体在出生后由于肾缺陷而死亡。引人注目的是，缺乏+KTS同种型的小鼠由于Sry表达水平的显著降低而显示出完全的XY性逆转。我们的数据表明两个剪接变体的不同功能，并将+KTS变体作为Sty在性别决定途径中的重要调节因子。
Alternative splicing of Wt1 results in the insertion or omission of the three amino acids KTS between zinc fingers 3 and 4. In vitro experiments suggest distinct molecular functions for + and -KTS isoforms. We have generated mouse strains in which specific isoforms have been removed. Heterozygous mice with a reduction of +KTS levels develop glomerulosclerosis and represent a model for Frasier syndrome. Homozygous mutants of both strains die after birth due to kidney defects. Strikingly, mice lacking +KTS isoforms show a complete XY sex reversal due to a dramatic reduction of Sry expression levels. Our data demonstrate distinct functions for the two splice variants and place the +KTS variants as important regulators for Sty in the sex determination pathway.