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Publication : Novel reporter alleles of GSK-3α and GSK-3β.

First Author  Barrell WB Year  2012
Journal  PLoS One Volume  7
Issue  11 Pages  e50422
PubMed ID  23185619 Mgi Jnum  J:195008
Mgi Id  MGI:5475429 Doi  10.1371/journal.pone.0050422
Citation  Barrell WB, et al. (2012) Novel reporter alleles of GSK-3alpha and GSK-3beta. PLoS One 7(11):e50422
abstractText  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-3beta and overlook the closely related protein GSK-3alpha. Here, we describe novel GSK-3alpha and GSK-3beta mouse alleles that allow us to visualise expression of their respective mRNAs by tracking beta-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-3alpha creates a Cre-dependent tissue-specific knockout. As expected, GSK3alpha mutants were viable, while GSK3beta mutants died after birth with a complete cleft palate. We also assessed the GSK-3alpha mutants for cranial and sternal phenotypes and found that they were essentially normal. Finally, we observed gestational lethality in compound GSK-3beta(-/-); GSK3alpha(+/-) mutants, suggesting that GSK-3 dosage is critical during embryonic development.
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