Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme
Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme
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DOI：
10.1016/j.ydbio.2005.12.034
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发表时间：
2006-03-15
影响因子：
2.7
通讯作者：
Bates, CM
中科院分区：
文献类型：
--
作者：
Poladia, DP;Kish, K;Bates, CM
为了确定成纤维细胞生长因子受体（fgfrs）1和2在后肾间充质中的重要性，我们产生了条件性敲除小鼠（fgfr 1/2（Mes-/-））。Fgfr 1（Mes-/-）和fgfr 2（Mes-/-）小鼠发育出外观正常的肾脏。两种受体（fgfr 1/2（Mes-/-））的缺失导致肾发育不全。Fgfr 1/2（Mes-/-）小鼠发育出输尿管芽（偶尔为异位芽），但不伸长或形成分支，且小鼠未发育出明显的后肾间充质。通过原位杂交，输尿管芽附近的突变间充质区域表达Eya 1和Six 1，但不表达Six 2、Sall 1或Pax 2，而输尿管芽正常表达Ret和Pax 2。异常高的凋亡率和相对较低的增殖率存在于突变体输尿管芽背侧的突变体间充质中，在胚胎日（E）10.5，而突变体输尿管芽组织经历了E11.5的高凋亡率。因此，fgfr 1和fgfr 2一起对后肾间充质的正常形成至关重要。在fgfr 1/2（Mes-/-）小鼠中，输尿管芽在开始时不伸长或分支。在后肾间充质雏形中，fgfr 1和fgfr 2似乎在Eya 1和Six 1的下游发挥作用，但在Six 2、Sall 1和Pax 2的上游发挥作用。最后，这是在条件性基因敲除模型中的第一例肾发育不全。(C)2005年爱思唯尔公司All rights reserved.
To determine the importance of fibroblast growth factor receptors (fgfrs) 1 and 2 in the metanephric mesenchyme, we generated conditional knockout mice (fgfr1/2(Mes-/-)). Fgfr1(Mes-/-) and fgfr2(Mes-/-) mice develop normal-appearing kidneys. Deletion of both receptors (fgfr1/2(Mes-/-)) results in renal aplasia. Fgfr1/2(Mes-/-) mice develop a ureteric bud (and occasionally an ectopic, bud) that does not elongate or branch, and the mice do not develop an obvious metanephric mesenchyme. By in situ hybridization, regions of mutant mesenchyme near the ureteric bud(s) express Eya1 and Six1, but not Six2, Sall1, or Pax2, while the ureteric bud expresses Ret and Pax2 normally. Abnormally high rates of apoptosis and relatively low rates of proliferation are present in mutant mesenchyme dorsal to the mutant ureteric bud at embryonic day (E) 10.5, while mutant ureteric bud tissues undergo high rates of apoptosis by E11.5. Thus, fgfr1 and fgfr2 together are critical for normal formation of metanephric mesenchyme. While the ureteric bud(s) initiates, it does not elongate or branch in fgfr1/2(Mes-/-) mice. In metanephric mesenchymal rudiments, fgfr1 and fgfr2 appear to function downstream of Eya1 and Six1, but upstream of Six2, Sall1, and Pax2. Finally, this is the first example of renal aplasia in a conditional knockout model. (C) 2005 Elsevier Inc. All rights reserved.