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

William B Barrell | Heather L Szabo-Rogers | Karen J Liu
PloS one | 2012

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.

Pubmed ID: 23185619

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/E013872/1
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/E013872
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/I021922/1
  • Agency: Wellcome Trust, United Kingdom
    Id: WT081880AIA
  • Agency: Wellcome Trust, United Kingdom

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Sanger Mouse Resources Portal (tool)

RRID:SCR_006239

Database of mouse research resources at Sanger: BACs, targeting vectors, targeted ES cells, mutant mouse lines, and phenotypic data generated from the Institute''''s primary screen. The Wellcome Trust Sanger Institute generates, characterizes, and uses a variety of reagents for mouse genetics research. It also aims to facilitate the distribution of these resources to the external scientific community. Here, you will find unified access to the different resources available from the Institute or its collaborators. The resources include: 129S7 and C57BL6/J bacterial artificial chromosomes (BACs), MICER gene targeting vectors, knock-out first conditional-ready gene targeting vectors, embryonic stem (ES) cells with gene targeted mutations or with retroviral gene trap insertions, mutant mouse lines, and phenotypic data generated from the Institute''''s primary screen.

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Pompep (tool)

RRID:SCR_010536

FTP site to access Schizosaccharomyces pombe protein data.

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International Mouse Phenotyping Consortium (IMPC) (tool)

RRID:SCR_006158

Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.

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