Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA‐2 in urogenital development
Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA‐2 in urogenital development
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DOI：
10.1093/emboj/17.22.6689
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发表时间：
1998-11
期刊：
影响因子：
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通讯作者：
Yinghui Zhou;K. Lim;K. Onodera;Satoru Takahashi;J. Ohta;N. Minegishi;F. Tsai;S. Orkin;Masayuki Yamamoto;J. D. Engel
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文献类型：
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作者：
Yinghui Zhou;K. Lim;K. Onodera;Satoru Takahashi;J. Ohta;N. Minegishi;F. Tsai;S. Orkin;Masayuki Yamamoto;J. D. Engel
导致胚胎或出生后早期致死性的突变可以掩盖任何基因在不相关和时间上不同的发育途径中的活动。转录因子加塔-2基因的靶向失活导致造血功能衰竭导致妊娠中期死亡。我们在这里表明，一个250 kbp的加塔-2酵母人工染色体（YAC）在原始和定型造血区室中强烈表达，而两个较小的YAC则没有。这种最大的YAC还在体外和体内挽救造血，从而将造血调节顺式元件定位于加塔-2结构基因的100和150 kbp 5′之间。将YAC转基因引入加塔-2−/−遗传背景中可使胚胎完成妊娠;然而，新生的获救幼崽很快死于致命的输尿管积水，并显示出一系列复杂的泌尿生殖系统异常。这些发现揭示了加塔-2在泌尿生殖系统和造血系统发育中起着同样重要的作用。
Mutations resulting in embryonic or early postnatal lethality could mask the activities of any gene in unrelated and temporally distinct developmental pathways. Targeted inactivation of the transcription factor GATA‐2 gene leads to mid‐gestational death as a consequence of hematopoietic failure. We show here that a 250 kbp GATA‐2 yeast artificial chromosome (YAC) is expressed strongly in both the primitive and definitive hematopoietic compartments, while two smaller YACs are not. This largest YAC also rescues hematopoiesis in vitro and in vivo, thereby localizing the hematopoietic regulatory cis element(s) to between 100 and 150 kbp 5′ to the GATA‐2 structural gene. Introducing the YAC transgene into the GATA‐2−/− genetic background allows the embryos to complete gestation; however, newborn rescued pups quickly succumb to lethal hydroureternephrosis, and display a complex array of genitourinary abnormalities. These findings reveal that GATA‐2 plays equally vital roles in urogenital and hematopoietic development.