Novel reporter alleles of GSK-3α and GSK-3β.
Novel reporter alleles of GSK-3α and GSK-3β.
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DOI：
10.1371/journal.pone.0050422
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu KJ
中科院分区：
文献类型：
--
作者：
Barrell WB;Szabo-Rogers HL;Liu KJ
糖原合成酶激酶3 （GSK-3）在发育、生理和疾病中起着关键作用。正因为如此，GSK-3抑制剂被越来越多地用于各种应用。此外，大多数分析都集中在GSK-3β上，而忽略了与其密切相关的蛋白GSK-3α。在这里，我们描述了新的GSK-3α和GSK-3β小鼠等位基因，使我们能够通过跟踪β-半乳糖苷酶活性来可视化其各自mrna的表达。我们使用这些新的lacZ等位基因比较了上颚和颅缝中的表达，发现确实存在差异表达。此外，两者都是功能缺失的等位基因，可用于产生纯合突变小鼠；此外，从GSK-3α中切除lacZ盒会产生cre依赖的组织特异性敲除。正如预期的那样，GSK3α突变体存活，而GSK3β突变体在出生后死亡，并伴有完全性腭裂。我们还评估了GSK-3α突变体的颅骨和胸骨表型，发现它们基本上是正常的。最后，我们观察复方GSK-3β−/−的妊娠致死性；GSK3α+/−突变，表明GSK-3剂量在胚胎发育过程中至关重要。
Glycogen Synthase Kinase 3 (GSK-3) is a key player in development, physiology and disease. Because of this, GSK-3 inhibitors are increasingly being explored for a variety of applications. In addition most analyses focus on GSK-3β and overlook the closely related protein GSK-3α. Here, we describe novel GSK-3α and GSK-3β mouse alleles that allow us to visualise expression of their respective mRNAs by tracking β-galactosidase activity. We used these new lacZ alleles to compare expression in the palate and cranial sutures and found that there was indeed differential expression. Furthermore, both are loss of function alleles and can be used to generate homozygous mutant mice; in addition, excision of the lacZ cassette from GSK-3α creates a Cre-dependent tissue-specific knockout. As expected, GSK3α mutants were viable, while GSK3β mutants died after birth with a complete cleft palate. We also assessed the GSK-3α mutants for cranial and sternal phenotypes and found that they were essentially normal. Finally, we observed gestational lethality in compound GSK-3β−/−; GSK3α+/− mutants, suggesting that GSK-3 dosage is critical during embryonic development.
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影响因子：
64.8
作者：
Skarnes WC;Rosen B;West AP;Koutsourakis M;Bushell W;Iyer V;Mujica AO;Thomas M;Harrow J;Cox T;Jackson D;Severin J;Biggs P;Fu J;Nefedov M;de Jong PJ;Stewart AF;Bradley A
通讯作者：
Bradley A
影响因子：
5.3
作者：
Patel, Satish;Doble, Bradley W.;Woodgett, James R.
通讯作者：
Woodgett, James R.
影响因子：
11.8
作者：
Doble, Bradley W.;Patel, Satish;Woodgett, James R.
通讯作者：
Woodgett, James R.
影响因子：
5.3
作者：
Hurtado, David E.;Molina-Porcel, Laura;Lee, Virginia M. -Y.
通讯作者：
Lee, Virginia M. -Y.
影响因子：
2.5
作者：
He, Fenglei;Popkie, Anthony P.;Xiong, Wei;Li, Lu;Wang, Ying;Phiel, Christopher J.;Chen, Yiping
通讯作者：
Chen, Yiping