Generation and Characterization of EphA1 Receptor Tyrosine Kinase Reporter Knockout Mice
Generation and Characterization of EphA1 Receptor Tyrosine Kinase Reporter Knockout Mice
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DOI：
10.1002/dvg.20434
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发表时间：
2008-10-01
期刊：
影响因子：
1.5
通讯作者：
Boyd, Andrew W.
中科院分区：
文献类型：
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作者：
Duffy, Shannon L.;Coulthard, Mark G.;Boyd, Andrew W.
Eph受体酪氨酸激酶（RTK）是一个高度保守的信号蛋白家族，在成体和胚胎期的细胞迁移、粘附、凋亡和增殖中发挥作用。在这里，我们描述了一种敲入小鼠，其中EphA 1的表达被破坏通过插入一个内部核糖体进入位点（IRES）-人胎盘碱性磷酸酶（ALPP）报告盒到EphA 1基因的外显子II。这显示出成功敲除内源性EphA 1的表达并通过EphA 1启动子加强ALPP报告基因的表达。ALPP报告蛋白的染色显示小鼠组织中的上皮限制性表达模式。在EphA 1敲除小鼠中，鉴定了两种不同的表型：在类似于80%的纯合子成年小鼠中发现了表现为扭结尾的异常尾发育。第二个明显的异常存在于相似的18%的女性，其特征是子宫阴道内发育伴子宫阴道积水，由生殖道疏通过程中细胞对凋亡的抵抗引起。这些结果表明EphA 1在组织图案化和细胞凋亡诱导的凋亡过程中可能发挥作用。创世纪46：553-561，2008。(C)2008 Wiley-Liss，Inc.
Eph receptor tyrosine kinases (RTKs) are a highly conserved family of signaling proteins with functions in cellular migration, adhesion, apoptosis, and proliferation during both adult and embryonic life. Here, we describe a knock-in mouse in which EphA1 expression is disrupted via the insertion of an internal ribosome entry site (IRES)-human placental alkaline phosphatase (ALPP) reporter cassette into exon II of the EphA1 gene. This was shown to successfully knockout expression of endogenous EphA1 and enforce expression of the ALPP reporter by the EphA1 promoter. Staining for the ALPP reporter protein demonstrated an epithelially restricted expression pattern in mouse tissues. In EphA1 null mice, two separate phenotypes were identified: abnormal tail development manifesting as a kinky tail was found in similar to 80% of homozygous adults. A second, distinct abnormality present in similar to 18% of females was characterized by imperforate uterovaginal development with hydrometrocolpos and caused by a resistance of cells to apoptosis during reproductive tract canalization. These results indicate a possible role for EphA1 in tissue patterning and hormone-induced apoptotic processes. genesis 46:553-561, 2008. (C) 2008 Wiley-Liss, Inc.